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M A Crocq

Publications and source records attributed to M A Crocq.

At least 37 records · Page 2Linked to original sources
PubMed1996

Dopamine D3 receptor gene: organization, transcript variants, and polymorphism associated with schizophrenia.

DNA fragments from a genomic library were used to establish the partial structure of the human dopamine D3 receptor gene (DRD3). Its coding sequence contains 6 exons and stretches over 40,000 base pairs. The complete DRD3 transcript and three shorter variants, in which the second and/or third exon are deleted, were detected in similar proportions in brains from four controls and three psychiatric patients. The Msp I polymorphism was localized in the fifth intron of the gene, 40,000 base pairs downstream the Bal I polymorphism and a PCR-based method was developed for genotyping this polymorphism. The distribution of the Msp I and Bal I genotypes were not independent in 297 individuals (chi 2 = 10.5, df = 4, P = 0.03), but only a weak association was found between allele 1 of the Bal I polymorphism and allele 2 of the Msp I polymorphism (chi 2 = 3.99, df = 1, P = 0.04). The previously reported association between homozygosity at both alleles of the Bal I polymorphism and schizophrenia was presently maintained in an extended sample, comprising 119 DSM-III-R chronic schizophrenics and 85 controls (chi 2 = 5.3, df = 1, P = 0.02) and found more important in mal than in females. The presence of the Bal I allele 2 is associated with an early age at onset, particularly in males (df = 35, t value = 2.6, P = 0.014). In the same sample, allelic frequencies, genotype counts, and proportion of homozygotes for the Msp I polymorphism did not differ between schizophrenics and controls (chi 2 = 0.06, df = 1, P = 0.80, chi 2 = 0.22, df = 1, P = 0.90 and chi 2 = 0.16, df = 1, P = 0.69, respectively). The large distance of the Msp I polymorphism from the Bal I polymorphism and its localization in the 3' part of the gene may explain the discrepant results obtained with the two polymorphisms.

Animals↗
PubMed1996

Effect of antidepressant medication on morning and evening thyroid function tests during a major depressive episode.

BACKGROUND: This study sought to determine whether changes in thyroid function that may occur during antidepressant treatment are related to a direct effect of the drug on the thyroid axis or to a change in clinical state. METHODS: Morning and evening thyroid function was evaluated in 30 euthyroid inpatients who met DSM-IV criteria for major depressive episode, by determination of free triiodothyronine, free thyroxine, and thyrotropin levels before and after 8 AM and 11 PM protirelin challenges (200 micrograms intravenously), on the same day. Results at baseline were compared with those after 1 month of antidepressant treatment with either amitriptyline hydrochloride, fluoxetine hydrochloride, or toloxatone. RESULTS: Clinical efficacy and effects on thyroid function did not differ across the 3 antidepressant drugs. Compared with pretreatment values, significant reductions in basal serum 8 AM free thyroxine, 11 PM free thyroxine, and 8 AM free triiodothyronine levels and increases in 11 PM maximum increment in plasma thyrotropin level and the difference between 11 PM and 8 AM maximum increment in plasma thyrotropin values were observed in responders (n = 11) but not in partial responders (n = 6) or nonresponders (n = 13). Moreover, nonresponders exhibited lower pretreatment 11 PM thyrotropin values (basal and maximal increment above basal) than responders. CONCLUSIONS: The results suggest that (1) changes in thyroid function are related to clinical recovery rather than to a direct effect of the antidepressant drug and (2) patients with the lowest pretreatment evening thyrotropin secretion have the lowest rate of antidepressant response, and this may contribute to treatment resistance.

Adult↗
PubMed1995

Analysis of clozapine response and polymorphisms of the dopamine D4 receptor gene (DRD4) in schizophrenic patients.

We have examined the hypothesis that a variable number of tandem repeats in the third cytoplasmic loop of the dopamine D4 receptor influences clinical response to clozapine using a sample of 189 schizophrenic patients. Alleles of the 48-bp repeat, which range from two to ten copies in the normal human population, were analysed by the polymerase chain reaction using genomic DNA as template. Association between these alleles and response to clozapine was tested using the difference in pre- and post-treatment GAS scores as a measure of response. We found no statistically significant variation between genotypic groups and response by analysis of variance. We conclude that the variation of the number of 48-bp repeats alone does not determine response to clozapine. Larger studies are underway to determine if there is a more subtle relationship with sequence variation within the repeats or at other polymorphic sites within the gene that may provide evidence for a component of clozapine's action being at D4 receptors.

Alleles↗
PubMed1995

Multihormonal responses to apomorphine in mental illness.

The neuroendocrine responses to subcutaneous (SC) administration of the dopamine (DA) agonist apomorphine (APO) hydrochloride (0.75 mg) were studied in a large group of subjects: 110 drug-free inpatients with either DSM-III-R schizophrenia (SCZ, n = 46), schizoaffective disorder (SAD, n = 14), or major depressive episode (MDE, n = 50), plus 18 hospitalized controls. Compared to a saline test, APO induced a significant increase of growth hormone (GH), adrenocorticotropin (ACTH), and cortisol (COR) release and a decrease in prolactin (PRL) secretion. No change in thyrotropin (TSH) levels was observed. In the total sample the extents of ACTH, COR and GH responses were correlated, but in the group of 88 subjects who exhibit a normal GH stimulation this correlation disappeared. This discrepancy suggests that APO-induced ACTH and COR stimulation may be mediated by pathways different from those mediating GH stimulation. According to diagnostical categories, we found significant lower ACTH and COR stimulation in the schizophrenic group and in patients with SAD, compared with that among controls or depressed patients. We found also a significant difference between subgroups of schizophrenic patients. These results agree with the hypothesis that different aspects of psychosis might involve different subtypes of DA-receptors with different localizations and sensitivities.

Adrenocorticotropic Hormone↗
PubMed1995

Cytochrome P4502D6 genotype does not determine response to clozapine.

1. The atypical antipsychotic drug clozapine, used in the treatment of resistant schizophrenia, is metabolized partly by the hepatic cytochrome P450 enzyme CYP2D6. Two phenotypes with respect to the activity of the enzyme are recognized (extensive metabolisers (EM) and poor metabolisers (PM)), resulting from allelic variation in the gene, CYP2D6. 2. Genotype was determined in 123 schizophrenic patients currently being treated with clozapine, in order to determine if EM or PM status influences response to this drug. Patients were divided into responders and non-responders using the Global Assessment Scale, and genotyped for the A and B poor metaboliser mutations by digesting PCR products with HpaII or BstNI. 3. Fifty-nine patients were heterozygous for allele B and for allele A. Eight patients were determined as poor metabolisers since they were homozygous either for A and B. Poor metabolisers were equally distributed between responders and nonresponders and no correlation between CYP2D6 alleles and response to clozapine was found. 4. The results are consistent with recent findings showing that CYP1A2, rather than CYP2D6, is the major enzyme responsible for the metabolism of clozapine.

Alleles↗
PubMed1995

An association study of a neurotrophin-3 (NT-3) gene polymorphism with schizophrenia.

Since abnormalities of brain development play a role in the aetiology of schizophrenia, growth factors, known to play a role in neurodevelopment, such as neurotrophin-3 (NT-3), are therefore candidate genes for this disorder. The A3/147 bp allele of a dinucleotide repeat polymorphism in the promoter region of the NT-3 gene has been reported as occurring more frequently in a sample of Japanese schizophrenics compared to controls. We have determined the frequency of alleles of this polymorphism in 175 Caucasian schizophrenic patients and 147 control subjects. The patient and control samples showed no significant deviation from Hardy-Weinberg equilibrium and, in a test of allalleles, the patients and controls did not differ significantly in allele frequencies. However, the male schizophrenics were more likely than male controls to have the A3/147 bp allele (P = 0.029).

Alleles↗
PubMed1994

Influence of thyroid hormones on morning and evening TSH response to TRH in major depression.

The serum levels of thyroid hormones and thyrotropin (TSH) were evaluated before and after 8 PM and 11 PM thyrotropin-releasing hormone (TRH) challenges, on the same day, in 41 drug-free DSM-III-R euthyroid major depressed inpatients and 16 hospitalized controls. Depressed patients exhibited elevated circulating concentrations of thyroid hormones, which were associated with and may have contributed to the blunted TSH response to TRH. This was confirmed by: (a) higher basal levels (albeit not always statistically significant) of free triiodothyronine (FT3B) and free thyroxine (FT4B) at 8 AM and 11 PM in the depressed patient population compared with the controls; (b) lower basal levels of TSH in the depressed subjects (even though this was only statistically significant at the 11 PM sampling) compared with the controls; (c) blunted TSH response to TRH (delta TSH) in the depressed group (although this was only statistically significant at 11 PM) and blunted delta delta TSH values (differences between 11 PM-delta TSH and 8 AM-delta TSH).

Adult↗
PubMed1994

Sleep disorders in the elderly: depression and post-traumatic stress disorder.

We report on two studies of sleep in the elderly. (1) One hundred and ninety-eight Spanish outpatients aged over 65 who met ICD-10 criteria for either a depressive episode, a recurrent, or a persistent mood disorder were compared with a matched population of depressives aged under 55. Factorial analysis and multiple regression showed that sleep complaints in the older group correlated less with severity of depression and had a less stable response to pharmacological treatment. (2) Post-traumatic stress disorder (PTSD) symptoms and sleep complaints were studied in 817 World War II veterans from Alsace-Lorraine who had been forcibly drafted into the Wehrmacht and subsequently detained as prisoners of war in Russia. The diagnosis of PTSD was associated with more severe wartime stressors and long internment. Eighty percent of respondants still report recurrent distressing dreams of wartime or captivity events after over 45 years. We analyzed sleep complaints in two elderly populations. Part one describes a Spanish study which compared the nosological significance and treatment response of sleep complaints in depressives aged over 65 or under 55. In part two, we study sleep complaints in former Alsatian prisoners of war (POWs) and analyze the influence of previous stressors and the aging process.

Adult↗
PubMed1994

An association study of debrisoquine hydroxylase (CYP2D6) polymorphisms in schizophrenia.

The cytochrome P450 mono-oxygenases are a group of enzymes that metabolize a variety of exogenous and endogenous compounds, some of which are potentially toxic. Individual variations in the metabolism of potential toxins could influence susceptibility to disorders having genetic and environmental components, such as schizophrenia. The frequency of two common mutant alleles of the gene for the cytochrome P450 enzyme debrisoquine-4-hydroxylase (CYP2D6) was determined in 264 Caucasian schizophrenic patients and 217 controls, using the polymerase chain reaction and restriction enzyme digestions. The patient and control samples showed no significant deviation from Hardy-Weinberg equilibrium and the frequency of each mutant allele (CYP2D6A and CYP2D6B) did not differ between patients and controls.

Alleles↗
PubMed1993

Neuroendocrine profile of SDZ HDC-912 and OPC-4392, two new atypical antipsychotic drugs, in schizophrenic patients.

The aim of this study was to evaluate the effect on the activity of the hypothalamic-pituitary dopaminergic system of two new atypical antipsychotic drugs: the ergoline derivative SDZ HDC-912, which is a dopamine (DA) D2 receptor partial agonist; and the quinolinone derivative OPC-4392, which acts as an agonist at presynaptic DA autoreceptors and as an antagonist at post-synaptic D2 receptors. The effects of both compounds were compared to the effects of the benzamide derivative amisulpride. Prolactin (PRL) and growth hormone (GH) levels before and after challenge with apomorphine (Apo), a dopaminergic agonist, were determined after at least 2 weeks washout and again after 1 month of treatment in DSM-III-R schizophrenic inpatients. SDZ HDC-912 significantly decreased Apo-induced PRL inhibition, and tended to decrease PRL secretion and Apo-induced GH stimulation. OPC-4392 induced a significant decrease in baseline PRL and in Apo-induced PRL suppression, and a non-significant decrease in Apo-induced GH stimulation. The neuroendocrine profiles of these two compounds agree with their dopaminergic properties; however, the decrease in PRL basal level differentiates the two drugs from neuroleptic agents.

Adult↗
PubMed1992

Association between schizophrenia and homozygosity at the dopamine D3 receptor gene.

Disturbances in dopamine neurotransmission have been postulated to underlie schizophrenia. We report data from two independent studies of a BalI polymorphism in the dopamine D3 receptor gene in patients with schizophrenia. In both studies, more patients than controls were homozygous (p = 0.005, p = 0.008). When pooled data were analysed, this difference was highly significant (p = 0.0001) with a relative risk of schizophrenia in homozygotes of 2.61 (95% confidence intervals 1.60-4.26).

Adult↗
PubMed1992

Bio-clinical prevalence or non-prevalence of drug addiction over psychiatric symptomatology.

It has been found that opiate abusers once detoxified are afflicted with personality disorders. An attempt was made to test the origin of drug abuse by comparing a group of drug abusers with personality disorders diagnosed as borderline or schizotypal with a group of people suffering from similar personality disorders but who did not use drugs. The results of the test are discussed.

Adult↗
PubMed1992

[Unipolar-bipolar distinction. The genetic arguments].

The latest classifications of mood disorders, such as DSM III and ICD 10, differ from previous ones by emphasizing the bipolar-unipolar distinction. This fairly recent distinction now enjoys a wide consensus. It is supported mainly by family studies. The first works originated from the school of Kleist and Leonhard and were quickly followed by reports by Perris and Angst (1966). Studies that followed the publication of DSM III confirm that the prevalence of bipolar mood disorders is twice as high among first-degree relatives of bipolar probands when compared with those of unipolar probands. Family studies suggest that unipolar and bipolar disorders are distinct but still share some degree of genetic overlap. Other genetic approaches such as twin and adoption studies are less conclusive. Recent linkage studies with genomic markers (RFLPs) cannot directly support the validity of the bipolar-unipolar distinction. They suggest the role of a major gene locus, notably in the Xq27-Xq28 region, only in a limited number of bipolar pedigrees. Most mood disorders might involve a polygenic environment; in this context, a more limited number of factors could be associated with the polarity of the disorder.

Bipolar Disorder↗
PubMed1990

Noninvasive in vivo detection of a fluorinated neuroleptic in the human brain by 19F nuclear magnetic resonance spectroscopy.

A fluorinated long-acting neuroleptic (fluphenazine decanoate) was detected in the human brain by fluorine nuclear magnetic resonance spectroscopy (MRS). The MRS system used had a 3 Tesla magnetic field, corresponding to a frequency of 118 MHz for the fluorine nucleus (Bruker Medspec 3 Tesla, 60-cm magnet bore width). The spectra were obtained with a surface coil having a 10-cm diameter, which was centered alternatively on the frontal lobe and basal ganglia, and on the occipital lobe. The impregnation and elimination kinetics of fluphenazine were monitored during three sessions (4 hours, 5 days, and 11 days after injection of the compound). This technique can be usefully applied to the in vivo study of the pharmacokinetics and site of action of psychiatric compounds in man.

Adult↗
PubMed1990

Random number generation by normal, alcoholic and schizophrenic subjects.

Controls (N = 45), schizophrenics (N = 20) and alcoholics (N = 23) were asked to choose at random a number between 1 and 10, 100 times. The correlation matrices of five different randomization indices were used to study within group variation; these matrices were similar for the normal and alcoholic groups, but very different for the schizophrenic group. The differences between the three groups were studied by canonical analysis and, in terms of the canonical variables, the mean performance of the normal group is clearly discriminated from that of the alcoholic and schizophrenic subjects.

Adult↗
PubMedDate not supplied

BalI and MspI polymorphisms of the dopamine D3 receptor gene in African Blacks and Caucasians.

An exonic BalI polymorphism and an intronic MspI polymorphism of the dopamine D3 gene were genotyped in 101 Caucasians from the Alsace and in 56 people from the Congo. This is the first study of the BalI polymorphism in sub-Saharan Africa and the first population study of the MspI site. BalI allele 1 was rare in the Congo (0.12) whereas it is the most frequent allele in all studies in Europe and Asia. MspI allele 1 was also significantly less frequent in the Congolese (0.24) than in Caucasians (0.52). D3 gene alleles show different frequencies in sub-Saharan Africa and may be useful for population studies.

Alleles↗