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C Benkelfat

Publications and source records attributed to C Benkelfat.

At least 37 records · Page 2Linked to original sources
PubMed2000

Acute tyrosine depletion and alcohol ingestion in healthy women.

BACKGROUND: Recently we reported that, in vervet monkeys, ingestion of an amino acid mixture deficient in the catecholamine precursors, phenylalanine and tyrosine, produced a decrease in alcohol self-administration. We now report the results of a similar study in humans. METHODS: Three groups of healthy female social drinkers were administered a nutritionally balanced amino acid mixture (B, n = 13), a mixture deficient in the serotonin precursor, tryptophan (Trp-free, n = 14), or a phenylalanine/tyrosine deficient mixture (Phe/Tyr-free, n = 12). Six hours after administration of the amino acid mixture, alcohol ingestion was measured during a free-choice "Taste Test." RESULTS: Compared to the B mixture, Phe/Tyr-free, but not Trp-free, significantly decreased the ingestion of alcohol [p < 0.02]. Neither Phe/Tyr-free nor Trp-free significantly decreased orange juice ingestion or the self-reported "Liking" of either substance. Some subjects experienced transient nausea and/or regurgitated the amino acid mixtures, but excluding these subjects did not change the results. CONCLUSIONS: The results suggest that (a) Phe/Tyr-free may be a suitable method for investigating the role of catecholamines in the self-administration and subjective effects of alcohol, (b) acutely decreased catecholamine neurotransmission might disrupt mechanisms mediating alcohol self-administration, and (c) acutely decreased serotonin neurotransmission seems not to alter alcohol self-administration.

Adult↗
PubMed2000

Statistical mapping analysis of serotonin synthesis images generated in healthy volunteers using positron-emission tomography and alpha-[11C]methyl-L-tryptophan.

OBJECTIVES: To assess the suitability of analyzing functional images of brain serotonin (5-HT) synthesis with statistical parametric mapping (SPM), and to investigate further possible sex-related regional differences. DESIGN: Prospective study. PARTICIPANTS: Six healthy men and 5 healthy women. INTERVENTION: Participants' brains were scanned with positron-emission tomography (PET) after intravenous injection of alpha-[11C]methyl-L-tryptophan (alpha-[11C]MTrp). OUTCOME MEASURES: Tissue radioactivity images were converted into functional images using the Patlak plot approach, and analyzed with 2 methods for global normalization in the SPM program: proportional scaling and analysis of covariance (ANCOVA). RESULTS: The data structure suggests that PET alpha-[11C]MTrp data meet the criteria for analysis with SPM, and that the proportional scaling method is more appropriate than the ANCOVA method for normalization. Regional differences in 5-HT synthesis were identified between men and women, and the significance of these findings was supported by region of interest (ROI) analyses. CONCLUSION: SPM analyses of PET alpha-[11C]MTrp data may be of value for identifying regional differences in brain 5-HT synthesis between groups, and in investigating the effects of psychotropic drugs. Since we found regional differences between male and female subjects, men and women should not be grouped for data analysis in PET alpha-[11C]MTrp studies.

Adult↗
PubMed1999

Analysis of 14 CAG repeat-containing genes in schizophrenia.

Recently, it has been suggested that trinucleotide repeat-containing genes may be involved in the etiology of schizophrenia. This study was aimed at investigating putative associations between allelic variants or expansions of CAG repeat-containing genes (CAGrCG) and schizophrenia or its variability with respect to responsiveness to conventional neuroleptics. CAG repeat allelic variants of 14 expressed sequences were compared among three groups of subjects: neuroleptic-responder (R; n = 43) and neuroleptic-nonresponder (NR; n = 63) schizophrenic patients, and a control group (C; n = 122). No CAG expansions, in the range of those observed in neurodegenerative diseases, were identified in these 14 expressed sequences. The sizes of CAG repeat for the hGT1 gene were marginally different among the three groups of subjects (Kruskal-Wallis H (2, 456) = 10.48, Bonferroni corrected P = 0.047). Comparisons among the different groups indicated that neuroleptic responders have shorter alleles compared to controls (Mann-Whitney adjusted Z = -3.23, P = 0.0012). NR patients were not different from controls. These preliminary results suggest that the hGT1 gene, or a gene in its vicinity, may be involved in the etiology of schizophrenia or in modifying the disease phenotype with regard to outcome and/or neuroleptic responsiveness. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:694-699, 1999.

Adolescent↗
PubMed1999

Lack of association between the hSKCa3 channel gene CAG polymorphism and schizophrenia.

Genetic anticipation, a phenomenon characterized by increased severity of symptoms and earlier age at onset of a disease in successive generations, is believed to be present in schizophrenia. In several neurodegenerative diseases showing anticipation, the mutation causing the disease is an expanded trinucleotide repeat. Therefore, genes containing trinucleotide repeats prone to expansion have become a suitable family of candidate genes in schizophrenia. A human calcium-activated potassium channel gene (hSKCa3), possibly mapping to chromosome 22q11-13, a region previously linked to schizophrenia, was recently described. This gene contains two contiguous expressed CAG repeat stretches. Recently, long allelic variants of one of these CAG repeats were found to be overrepresented in schizophrenic patients compared to normal controls. In this study we attempted to replicate this result and to study the relationship between the length of this CAG repeat on the one hand and the severity and age at onset of the disease on the other hand. No association with the disease or correlation with the severity of schizophrenia was identified. In addition, hSKCa3 was mapped to chromosome 1. Our results do not support the involvement of this particular CAG repeat-containing gene in schizophrenia.

Adult↗
PubMed1999

Neural correlates of eye tracking deficits in first-degree relatives of schizophrenic patients: a positron emission tomography study.

BACKGROUND: Schizophrenia is thought to arise from the interaction of genetically mediated and environmentally triggered abnormalities in brain function. Reduced frontal activation, reported in schizophrenic patients, may be one expression of genetic risk. The present study investigated whether frontal activation in relatives of schizophrenic patients would be related to eye tracking deficits (ETD), which are considered a behavioral marker of risk for schizophrenia. METHODS: Subjects were first-degree relatives of schizophrenic patients (n = 17) and controls (n = 11). Relatives were divided into those with normal and abnormal pursuit based on qualitative ratings. Subjects were scanned using positron emission tomography and the H(2)15O bolus subtraction technique while performing smooth pursuit and fixation. Brain areas more active in pursuit than fixation were identified in the 3 groups. Correlations were used to investigate the relationship between activation of pursuit regions and pursuit gain in the relatives. RESULTS: Controls significantly activated frontal eye fields (FEFs) and posterior areas, including the motion processing area, V5, and cuneus. The 2 groups of relatives activated the same posterior regions as controls, but differed from each other in activation of FEFs. Relatives with normal tracking activated right dorsal FEFs while relatives with ETD did not. Individual subtractions revealed that 90% of controls and 100% of the relatives with normal tracking activated FEFs during pursuit compared with 42% of relatives with ETD (P = .009). Pursuit gain was significantly and selectively associated with percent activation of right dorsal FEFs (r = 0.74). CONCLUSIONS: Subtle frontal dysfunction seems to be a pathophysiological substrate of ETD in relatives of schizophrenic patients, and may be one aspect of genetically mediated differences in brain function relevant to schizophrenia.

Eye Movements↗
PubMed1999

Pet studies of serotonin synthesis in the human brain.

The method for measuring serotonin synthesis in human brain uses [11C]alpha-methyl-L-tryptophan as a tracer and positron emission tomography. The alpha-methyl-L-tryptophan is converted to alpha-methylserotonin, which is not a substrate for monoamine oxidase and therefore accumulates in the brain. In a pilot study published recently, rates of serotonin synthesis were found to be higher in men than in women. This was due to the lower plasma free tryptophan in the women under the experimental conditions used, and does not necessarily reflect the situation in all circumstances. Acute tryptophan depletion lowered brain serotonin synthesis by 90% or more. Patients with borderline personality disorder, who exhibit emotional lability and impulsivity, may have lower brain serotonin synthesis rates than healthy controls.

Brain↗
PubMed1999

A comparison of the effects of acute tryptophan depletion and acute phenylalanine/tyrosine depletion in healthy women.

Acute tryptophan depletion (ATD), which is thought to lower serotonin levels, can result in a lowering of mood. In the present study we compared the effect of ATD with acute phenylalanine/tyrosine depletion (APTD) in healthy women. Although considerable evidence relates catecholamines to the regulation of anxiety, there was no difference in anxiety responses in the ATD and APTD groups when the women underwent a mildly stressful psychological challenge. Both ATD and APTD caused a similar lowering of mood. Both depletions also increased heart rate. These results suggest that APTD is a useful method for studying the effect of low catecholamine levels in humans, and that catecholamines are involved in the regulation of mood.

Adult↗
PubMed1999

Acute tryptophan depletion in healthy young women with a family history of major affective disorder.

BACKGROUND: Acute tryptophan depletion (ATD), a means of reducing brain serotonin synthesis, lowers mood in normal males with a multi-generational family history of major affective disorder (MAD) and in normal women devoid of any family history of psychiatric illness. As both a family history of MAD and female sex are factors predisposing to depression, the hypothesis that a mood lowering response to ATD may reflect a susceptibility to depression was further investigated in young women with an extensive, multi-generational family history of MAD. In addition, the temporal stability of mood change following repeated trials of ATD was also assessed in this study. METHODS: To deplete tryptophan, a tryptophan deficient amino acid mixture was ingested on two separate occasions. The control treatment, administered on a third occasion, was a nutritionally balanced amino acid mixture containing tryptophan. RESULTS: A marked lowering of plasma tryptophan (85-90 %) was achieved by both depletions. In comparison to the balanced condition, family history positive (FH +) women showed no lowering of mood to either the first or second ATD (N = 13) and N = 12, respectively). Mood change between the two ATD trials (N = 13) exhibited poor temporal stability. CONCLUSIONS: These results may indicate that serotonin responsiveness is not an important characteristic of vulnerability to depression in these women. Alternately, these negative results may be due to the exclusion of a large number of FH + women who had already experienced an episode of depression, resulting in the selection of a biased FH + sample who are resistant to the mood lowering effects of ATD.

Adolescent↗
PubMed1999

Polyglutamine-containing proteins in schizophrenia.

Genetic anticipation, manifested by increased severity and earlier age-at-onset of the disease over successive generations, is reported in schizophrenia. The molecular basis of anticipation in several neurodegenerative diseases is unstable coding CAG repeat expansions. Anticipation was reported in schizophrenia. Recently, studies suggested that enlarged CAG/CTG repeats are over represented in schizophrenic patients compared to normal controls. Together, these observations suggest that unstable CAG repeats may play a role in the etiology of schizophrenia. The purpose of this study is to test for the presence of polyglutamine-expanded tracts, encoded by CAG repeats, in total protein extracts derived from lymphoblastoid cell lines of schizophrenic patients. Proteins from schizophrenic patients (n = 59) and normal controls (n = 73) were separated by means of SDS-polyacrylamide gel electrophoresis, wet blotted onto nitrocellulose membrane and probed with a monoclonal antibody (mab 1C2) recognizing expanded polyglutamine arrays. Three abnormal bands corresponding to protein(s) of molecular weight of approximately 50 kDa were identified in two unrelated schizophrenic patients and in a sibling of one of these patients. None of the normal controls tested positive for this abnormal band. These results suggest that expanded polyglutamine-containing proteins, though rare, may play a role in the pathogenesis of schizophrenia.

Age of Onset↗
PubMed1999

Behavioral disinhibition induced by tryptophan depletion in nonalcoholic young men with multigenerational family histories of paternal alcoholism.

OBJECTIVE: A deficit in serotonergic neurotransmission has been linked to impulsive behavior, as well as to disorders characterized by disinhibition. The present study tested the hypothesis that young men at high risk for alcoholism demonstrate greater behavioral disinhibition after acute dietary depletion of tryptophan, the amino acid precursor of serotonin. METHOD: A double-blind, placebo-comparison, between-subjects study design was used. Nonalcoholic young men with a multigenerational paternal family history of alcoholism (N = 13) or with no family history of alcoholism (N = 15) in two previous generations were administered mixtures of tryptophan-deficient amino acid to achieve plasma tryptophan depletion. Comparison subjects with a multigenerational paternal family history of alcoholism (N = 1) and comparison subjects with no family history of alcoholism (N = 18) were given a balanced mixture. Five hours after this, all were tested on a modified Taylor task and a go/ no-go task measuring aggressive response and disinhibition, respectively. RESULTS: Plasma tryptophan levels were reduced by 89% in both groups. Tryptophan depletion had no effect on aggressive response. In contrast, tryptophan-depleted individuals with a family history of alcoholism made more commission errors (responses to stimuli associated with punishment or loss of reward) than did tryptophan-depleted individuals with no family history of alcoholism and those receiving the balanced (comparison) mixture of amino acid in either group. CONCLUSIONS: Low serotonin levels may be implicated in the high disinhibition or impulsivity observed in some individuals with a genetic vulnerability to alcohol abuse or dependence.

Affect↗
PubMed1999

Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide.

OBJECTIVE: Postmortem studies have indicated that suicide victims have greater serotonin receptor 2A (5-HTR2A) binding in prefrontal brain regions. However, there remains some controversy regarding the biological specificity of these findings. The authors hypothesized that the variance observed in brain 5-HTR2A binding is genetically mediated, at least in part. METHOD: Postmortem data from 56 subjects who had committed suicide and 126 normal comparison subjects were studied; brain tissue was available from 11 subjects who committed suicide and 11 comparison subjects. Homogenate binding assays were carried out with [3H]ketanserin. Variation at the 5-HTR2A gene (HTR2A) was investigated by means of two polymorphisms: T102C and A-1438G. RESULTS: 5-HTR2A binding was greater in the prefrontal cortex of the subjects who committed suicide. In addition, the findings suggest that HTR2A variation significantly affects 5-HTR2A binding. However, no interaction between suicidal behavior and this locus was observed. CONCLUSIONS: These results confirm previous reports of greater 5-HTR2A binding in subjects who committed suicide; they also provide preliminary evidence suggesting that the number of 5-HTR2A receptors is genetically mediated.

Adult↗
PubMed1999

T102C polymorphism in the 5HT2A gene and schizophrenia: relation to phenotype and drug response variability.

Although genes play a major role in the etiology of schizophrenia, no major genes involved in this disease have been identified. However, several genes with small effect have been reported, though inconsistently, to increase the risk for schizophrenia. Recently, the 5HT2A 2 allele (T102C polymorphism) was reported to be over-represented in patients with schizophrenia. Other reports have found an excess of allele 2(C) only in schizophrenic patients who are resistant to clozapine, not in those who respond to clozapine. In this study, the 5HT2A receptor allele 2 frequencies were compared between 2 groups of patients with schizophrenia (39 responders and 63 nonresponders) based on long-term outcome and response to typical neuroleptics. A control group of 90 healthy volunteers screened for mental disorders was also included. Genotype 2/2 tended to be more frequent in patients with schizophrenia with poor long-term outcome and poor response to typical neuroleptics (Bonferroni corrected p = 0.09). This difference was significant in men (Bonferroni corrected p = 0.054) but not in women. In addition, the age at first contact with psychiatric care was significantly younger in the patients with schizophrenia with genotype 2/2 than in patients with genotype 1/1. These result suggest that the 5HT2A-receptor gene may play a role in a subset of schizophrenia characterized by poor long-term outcome and poor response to neuroleptics.

Adult↗
PubMed1999

[Postoperative infections after heart surgery under extracorporeal circulation].

Postoperative infection is still an important cause of mortality and morbidity after cardiac surgery. The aim of this study was to assess its incidence and causes in order to optimise treatment. Between January 1996 and December 1997, 1,000 consecutive patients (253 women and 747 men) were operated for cardiac aortic pathology under cardiopulmonary bypass. The mean age was 66 +/- 11 years. The initial pathology was coronary artery disease (N = 663), valvular heart disease (N = 193), an association of the two (N = 94), thoracic aortic pathology (N = 38) or other pathologies (N = 12). The global postoperative infection rate was 4.9% (N = 49). The incidence of sternal and/or mediastinal infections was 0.7%, of bronchopneumonia 0.9%, urinary infection 2.1%, and septicaemia 1.7%. Nine patients died of the consequences of an infection. The hospital stay was significantly longer in infected patients, irrespective of the site of infection. Statistical analysis of the whole population did not show any predictive factor related to the preoperative clinical status of the patients. The only predictive factor demonstrated was the day on which surgery was performed: the infection rate in patients operated during the first 4 days of the week was 2.2% compared with 7.3% for the patients operated during the last 3 days (p = 0.004, odds ratio (OR) = 3.57). In those patients who had an urinary infection, the two identified risk factors were the female gender (p = 0.006, OR = 3.34) and an operation performed at the end of the week (p = 0.017, OR = 3.77). In patients with sternal and medistinal infections, the only identified predictive factor was combined coronary artery and valvular surgery (p = 0.009, OR = 7.43). With respect to pulmonary infections, the only predictive factor was recent preoperative myocardial infarction (< 1 month) (p = 0.004, OR = 7.5). Finally, no predictive risk factors were identified in those patients who developed septicaemia. In conclusion, this study showed that postoperative infection remains a serious complication of cardiac surgery. The prevention of these complications should be a priority for quality health care.

Adult↗
PubMed1998

Regional cerebral metabolic asymmetries replicated in an independent group of patients with panic disorders.

BACKGROUND: Abnormal left/right (L/R) hemispheric ratios of regional cerebral glucose metabolic rates (rCMRglc) (hippocampus and inferior prefrontal cortex) have been noted in unmedicated panic disorder patients. METHODS: An independent group of panic disorder patients placed on imipramine was studied with positron-emission tomography, testing for evidence of normalization versus persistence of the abnormal rCMRglc ratios. Differences in orbital frontal rCMRglc values between the imipramine-treated and the previously reported unmedicated panic disorder patients were tested examining for evidence that the differences would resemble those noted in obsessive-compulsive disorder (OCD) patients treated with clomipramine. RESULTS: We found the same abnormally low L/R hippocampal and posterior inferior prefrontal rCMRglc ratios in the imipramine-treated panic disorder patients. In addition, we found posterior orbital frontal rCMRglc decreases in the imipramine-treated panic disorder patients compared with the unmedicated panic disorder patients. CONCLUSIONS: These abnormal asymmetries found in unmedicated panic disorder patients and now in imipramine-treated panic disorder patients may reflect a trait abnormality. The orbital frontal rCMRglc differences between the imipramine-treated and unmedicated patients are similar to changes noted in OCD patients treated with clomipramine and may reflect direct or indirect effects of imipramine treatment in panic disorder patients.

Adult↗
PubMed1998

Tryptophan depletion, executive functions, and disinhibition in aggressive, adolescent males.

Low serotonin has been associated with aggressive behavior and impulsivity. Executive functions (cognitive abilities involved in the initiation/maintenance of goal attainment) have also been related to aggression. We tested whether dietary depletion of tryptophan, the amino acid precursor of serotonin, would increase disinhibition (impulsivity) in aggressive male adolescents. Cognitive-neuropsychological variables predictive of disinhibition were explored. Stable aggressive and nonaggressive adolescent men received balanced and tryptophan-depleted, amino acid mixtures separately (counterbalanced, double-blind). Commission errors on a go/no-go learning task (i.e., failures to inhibit responding to stimuli associated with punishment/nonreward) measured disinhibition. Aggressive adolescent males made more commission errors as compared to nonaggressives. Lower executive functioning was significantly related to commission errors over and above conventional memory abilities. Tryptophan depletion had no effect on commission errors in the aggressive adolescents, possibly because of a ceiling effect.

Adolescent↗
PubMed1998

Validation of a less-invasive method for measurement of serotonin synthesis rate with alpha-[11C]methyl-tryptophan.

We tested in normal human subjects a less invasive method to obtain plasma input function required in the calculation of the brain serotonin synthesis rate measured with positron emission tomography (PET) and alpha-[11C]methyl-tryptophan (alpha-MTrp). The synthesis rates derived with the arterial input function were compared to those derived from venous plasma and venous sinus time-radioactivity curves obtained from dynamic PET images. Dynamic PET images were obtained for the lengths up to 90 minutes after an injection of alpha-MTrp (400 to 800 MBq). Input functions were generated from both artery and vein in three subjects, and from artery only in two subjects. Net unidirectional uptake constants of alpha-MTrp (K*; mL/g/min) were calculated in several brain regions graphically using data between 20 and 60 minutes after injection with different input functions. In the five subjects with arterial sampling, we tested two methods for correcting the input functions from the venous samples: (1) normalization to the mean exposure time at 20 minutes from arterial curve; and (2) the use of the venous sinus curve for the first 20 minutes. Venous curves coincided with the arterial ones after about 20 minutes. When the venous curves were used, there was an underestimation of the area under the curves up to 20 minutes, resulting in a 5% to 30% overestimation of K* values. Combined use of the sinus curve up to 20 minutes and venous curve from 20 to 60 minutes as an input function resulted in the K* (mL/g/min) values larger by 7.1 +/- 3.8% than the K* values estimated with the arterial input function. Normalization of the venous curve to the exposure time at 20 minutes obtained from the arterial plasma curve resulted in a bias in the K* of about -0.34 +/- 3.32%. The bias from the K* values was propagated to the serotonin synthesis rates. The use of a combination of the venous blood samples and venous sinus as the input function resulted in an acceptable bias in the serotonin synthesis rates from the tissue time-radioactivity curves generated by PET.

Adult↗