23 results on '"Benkelfat, C."'
Search Results
2. List of Contributors
- Author
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Alves, C.J., primary, Anglard, P., additional, Anier, K., additional, Armstrong, R.A., additional, Bachtell, R.K., additional, Bakshi, K., additional, Barbanti, P., additional, Barrio, P., additional, Batalla, A., additional, Becker, J.B., additional, Bekker, A., additional, Benkelfat, C., additional, Bergman, J., additional, Bhattacharya, P., additional, Bisagno, Veronica, additional, Brimijoin, S., additional, Brown, Z.J., additional, Buffalari, D., additional, Bühler, K.-M., additional, Caffino, L., additional, Cafforio, G., additional, Camarini, R., additional, Carvalho, V.M., additional, Cepko, L.C.S., additional, Chen, C.-C., additional, Chu, X.-P., additional, Corbit, L.H., additional, Crofton, E.J., additional, Crunelle, C.L., additional, Cunha, P.J., additional, Cunha-Oliveira, T., additional, Currie, P.J., additional, D’Ascenzo, M., additional, Dieckmann, L.H.J., additional, von Diemen, L., additional, Dumont, E.C., additional, Eagle, A.L., additional, Eipper, B.A., additional, Eipper-Mains, J.E., additional, Engeln, M., additional, Erb, S., additional, Farré, A., additional, Farré, M., additional, Felts, A.S., additional, Fofi, L., additional, Foster, J.D., additional, Fox, H.C., additional, Frankfurt, M., additional, Freissmuth, M., additional, Fuchs, R.A., additional, Fumagalli, F., additional, Gajewski, P.A., additional, Galaj, E., additional, Galduróz, J.C.F., additional, Garling, E.E., additional, Gentile, T.A., additional, Giannotti, G., additional, Girault, J.-A., additional, Glass, J.D., additional, Goncalves, P.D., additional, González-Duarte, A., additional, Gonzalez-Nunez, V., additional, Gould, R.W., additional, Grassi, C., additional, Green, T.A., additional, Green-Sadan, T., additional, Gu, H.H., additional, Guan, Xiaowei, additional, Halbout, B., additional, Han, D.D., additional, Henry, L.K., additional, Pérez de Heredia, J.L., additional, Higginbotham, J.A., additional, Hofmaier, T., additional, Holy, M., additional, Hsu, K.-S., additional, Huang, C.-C., additional, James, J., additional, Jones, A.W., additional, Jones, C.K., additional, Kalda, A., additional, Kearns, D.N., additional, Kerver, H.N., additional, Kessler, F., additional, Kohut, S.J., additional, Krnjević, K., additional, Kucab, P., additional, Kudlacek, O., additional, Kupferschmidt, D.A., additional, Kuzhikandathil, E.V., additional, Lee, M.R., additional, Leggio, L., additional, Lever, J.R., additional, Lever, S.Z., additional, Leyton, M., additional, Li, J.-X., additional, Lima, D.R., additional, Lobo, M.K., additional, López-Moreno, J.A., additional, López-Pelayo, H., additional, Lovejoy, D.A., additional, Luf, A., additional, Lugon, M.D.M.V., additional, Lyons, C.E., additional, Magalhães, A., additional, Magalhães, P.V.S., additional, Mainardi, M., additional, Mains, R.E., additional, Mantsch, J.R., additional, Marcourakis, T., additional, Marhe, R., additional, Matthys, F., additional, El Mestikawy, S., additional, Milivojevic, V., additional, Miller, D.K., additional, Min, M.O., additional, Minnes, S., additional, Mitchell, M.R., additional, Monteiro, P.R., additional, Murthy, V., additional, Muschamp, J.W., additional, Nagy, C., additional, Nakamura-Palacios, E.M., additional, Narvaez, J.C.M., additional, Normandeau, C.P., additional, Ornell, F., additional, Orsini, C.A., additional, Ostlund, S.B., additional, Otkins, J., additional, Patel, V.B., additional, Pelição, F.S., additional, Pereira, S.P., additional, Peres, M.D., additional, Potenza, M.N., additional, Preedy, V.R., additional, Prosser, R.A., additional, Quednow, B.B., additional, Rajendram, R., additional, Ramos, A.C., additional, Ranaldi, R., additional, Rangel-Barajas, C., additional, Rebec, G.V., additional, Robison, A.J., additional, Rodríguez, R.E., additional, Rohn, M.C.H., additional, Roth-Deri, I., additional, Scala, S.G., additional, Scavone, C., additional, Schellekens, A., additional, Scherer, J., additional, Schmid, R., additional, Scurlock, R.D., additional, Setlow, B., additional, Simmons, S.J., additional, Singer, L.T., additional, Sinha, R., additional, Sitte, H.H., additional, Smart, K., additional, Stockner, T., additional, Summavielle, T., additional, Szumlinski, K.K., additional, Tanda, G., additional, Torrens, M., additional, Tunstall, B.J., additional, Urbano, F.J., additional, Vaughan, R.A., additional, Verhaeghe, M., additional, Vonmoos, M., additional, Wagner, J.J., additional, Wang, Y., additional, Xi, Z.-X., additional, Xu, Y., additional, Yadid, G., additional, Ye, J.-H., additional, Yoon, S., additional, Zallar, L.J., additional, Zhan, Chang-Guo, additional, Zhang, H.-Y., additional, Zhang, Y., additional, Zheng, Fang, additional, Zuo, W., additional, and Zwiller, J., additional
- Published
- 2017
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3. Reduced dopamine response to amphetamine in subjects at ultra-high risk for addiction.
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Casey KF, Benkelfat C, Cherkasova MV, Baker GB, Dagher A, and Leyton M
- Subjects
- Case-Control Studies, Central Nervous System Stimulants pharmacology, Corpus Striatum diagnostic imaging, Corpus Striatum metabolism, Dopamine Antagonists, Female, Functional Neuroimaging, Humans, Male, Positron-Emission Tomography, Prodromal Symptoms, Raclopride, Substance-Related Disorders diagnostic imaging, Young Adult, Amphetamine pharmacology, Dopamine metabolism, Family Health, Substance-Related Disorders diagnosis
- Abstract
Background: Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use problems. In part, this might reflect perturbed mesolimbic dopamine responses., Methods: We measured amphetamine-induced changes in [(11)C]raclopride binding in 1) high-risk young adults with a multigenerational FH of substance use disorders (n = 16); 2) stimulant drug-naïve healthy control subjects with no known risk factors for addiction (n = 17); and 3) subjects matched to the high-risk group on personal drug use but without a FH of substance use problems (n = 15)., Results: Compared with either control group, the high-risk young adults with a multigenerational FH of substance use disorders exhibited smaller [(11)C]raclopride responses, particularly within the right ventral striatum. Past drug use predicted the dopamine response also, but including it as a covariate increased the group differences., Conclusions: Together, the results suggest that young people at familial high risk for substance use disorders have decreased dopamine responses to an amphetamine challenge, an effect that predates the onset of addiction., (© 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.)
- Published
- 2014
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4. The effects of age and estrogen on stress responsivity in older women.
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Dumas JA, Albert KM, Naylor MR, Sites CK, Benkelfat C, and Newhouse PA
- Subjects
- Age Factors, Aged, Aged, 80 and over, Female, Humans, Middle Aged, Psychiatric Status Rating Scales, Psychological Tests, Affect drug effects, Estradiol pharmacology, Postmenopause drug effects, Stress, Psychological psychology
- Abstract
Objective: The current study examined whether age after menopause impacted the effect of estradiol (E2) on mood after a psychosocial stress manipulation., Background: Previous studies have shown that E2 improves mood in women around the menopause transition but does not improve mood for older postmenopausal women. We have previously shown that E2 treatment in nondepressed women resulted in increased negative mood after psychosocial stress., Design: Participants were 22 postmenopausal women placed on either oral placebo or 17β-estradiol (1 mg/day for 1 month, then 2 mg/day for 2 months)., Method: At the end of the 3-month treatment phase, the participants performed the Trier Social Stress Test followed by mood ratings. To examine the effects of age on the estrogen-stress interaction, we performed a median split on age and created four groups of participants: younger-placebo (mean age: 55.5 years), younger-E2 (mean age: 55.5 years), older-placebo (mean age: 73.0 years), and older-E2 (mean age: 76.8 years)., Results: : The results showed that both older and younger E2-treated participants exhibited a significant and similar increase in negative mood after psychosocial stress compared with placebo-treated women., Conclusions: These results suggest that E2 may play a significant role in modulating emotional reactivity to stressful events and that this effect persists in older women. Furthermore, responsivity to E2 effects on emotional processing appears to be intact even years after menopause in contrast with other cognitive and behavioral effects of E2, which may be limited to the early postmenopausal years.
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- 2012
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5. Perinatal effects on in vivo measures of human brain serotonin synthesis in adulthood: a 27-year longitudinal study.
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Booij L, Benkelfat C, Leyton M, Vitaro F, Gravel P, Lévesque ML, Arseneault L, Diksic M, and Tremblay RE
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- Adult, Birth Weight physiology, Brain diagnostic imaging, Carbon Radioisotopes, Female, Heart Diseases etiology, Heart Diseases pathology, Humans, Longitudinal Studies, Lung Diseases etiology, Lung Diseases pathology, Male, Nicotine adverse effects, Positron-Emission Tomography, Pregnancy, Prenatal Exposure Delayed Effects pathology, Stress, Psychological etiology, Stress, Psychological pathology, Surveys and Questionnaires, Tryptophan analogs & derivatives, Brain metabolism, Brain pathology, Obstetric Labor Complications pathology, Serotonin metabolism
- Abstract
There is an increasing evidence that prenatal and early postnatal stressors have life long impacts on physical and mental health problems. Animal studies have shown that this could include enduring changes to brain serotonin neurotransmission. In the present study, we tested whether perinatal adversity in humans has a long-term impact on brain serotonin neurotransmission in adulthood. Twenty-six healthy males, recruited from a 27-year longitudinal study, underwent a positron emission tomography scan with the tracer alpha-[¹¹C]methyl-L-tryptophan (¹¹C-AMT), as an index of serotonin synthesis capacity. The trapping constant is taken as a proxy for the regional 5-HT synthesis. Birth complications, especially a delivery where the fetus showed signs of physiological distress, predicted lower ¹¹C-AMT trapping in the hippocampus and medial orbitofrontal cortex. Lower ¹¹C-AMT trapping in the medial orbitofrontal cortex was also predicted by maternal smoking and lower birth weight. There were no effects of childhood or recent adversity. This is the first human study reporting associations between perinatal adversity and adult ¹¹C-AMT trapping in the hippocampus and medial orbitofrontal cortex. The associations suggest that limbic serotonin pathways may be particularly vulnerable to environmental challenges during the period when they undergo the most prominent neurodevelopmental changes. In combination with other risk factors, perinatal stressors may contribute to increased vulnerability for psychiatric disorders in which serotonin plays a major role., (Copyright © 2011 Elsevier B.V. All rights reserved.)
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- 2012
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6. Striatal dopamine responses to intranasal cocaine self-administration in humans.
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Cox SM, Benkelfat C, Dagher A, Delaney JS, Durand F, McKenzie SA, Kolivakis T, Casey KF, and Leyton M
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- Basal Ganglia diagnostic imaging, Cocaine pharmacokinetics, Female, Humans, Hydrocortisone blood, Male, Phenylalanine blood, Positron-Emission Tomography, Putamen diagnostic imaging, Putamen metabolism, Raclopride administration & dosage, Raclopride metabolism, Receptors, Dopamine D2 metabolism, Self Administration, Tyrosine blood, Young Adult, Administration, Intranasal, Basal Ganglia metabolism, Cocaine administration & dosage, Cocaine pharmacology, Dopamine metabolism
- Abstract
Background: The effect of self-administered cocaine on extracellular dopamine (DA) levels has not been measured in humans., Methods: Ten nondependent cocaine users underwent positron emission tomography [11C]raclopride scans following intranasal self-administration of cocaine hydrochloride (1.0 mg/kg) and placebo powder., Results: Compared with placebo, intranasal cocaine self-administration decreased [11C]raclopride binding values in the ventral limbic striatum and putamen. Individual differences in the magnitude of the [11C]raclopride response in the ventral striatum were predicted by lifetime histories of stimulant drug use., Conclusions: The results suggest that 1) intranasal cocaine self-administration increases synaptic DA levels in human striatum and 2) prior use of stimulant drugs on the street is associated with progressively greater cocaine-induced DA responses. These dopaminergic effects might influence susceptibility to drug-seeking behavior and the progression to substance abuse.
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- 2009
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7. CTN-194 (PICCO): design of a trial of citalopram for the prevention of depression and its consequences in HIV-hepatitis C co-infected individuals initiating pegylated interferon/ribavirin therapy.
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Klein MB, Cooper C, Brouillette MJ, Sheehan NL, Benkelfat C, Annable L, Weston F, Kraus D, and Singer J
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- Canada, Depression etiology, Double-Blind Method, Drug Therapy, Combination, HIV Infections drug therapy, Hepatitis C drug therapy, Humans, Interferon alpha-2, Psychometrics, Recombinant Proteins, Sample Size, Severity of Illness Index, Treatment Outcome, Antidepressive Agents, Second-Generation therapeutic use, Antiviral Agents therapeutic use, Citalopram therapeutic use, Depression drug therapy, HIV Infections psychology, Hepatitis C psychology, Interferon-alpha therapeutic use, Ribavirin therapeutic use
- Abstract
Hepatitis C (HCV)-related end stage liver disease is a primary cause of morbidity and mortality in people with HIV. Despite this, co-infected patients have low rates of HCV treatment initiation and completion. This is in large part due to the risk of pegylated-interferon alpha (PEG-IFN-alpha)-related neuropsychiatric complications. We describe the design of a multicentre randomized, placebo-controlled trial that evaluates whether antidepressant prophylaxis is superior to early detection and treatment of depression in increasing the successful completion of HCV therapy. Seventy-six HIV+ adults with chronic HCV infection requiring therapy and with no contraindications to PEG-IFN-alpha/ribavirin will be randomized in a 1:1 ratio to receive citalopram or placebo starting three weeks prior to HCV treatment. A novel aspect of the trial design is the built-in management of emergent depression while maintaining the blinded treatment assignment. This will permit the comparison of prophylactic versus therapeutic use of citalopram. The primary outcome is the average proportion of prescribed PEG-IFN-alpha and ribavirin doses taken per month at weeks 12 and 24, and will be compared between treatment arms. The study will also compare the development of moderate-to-severe depression between treatment arms. A unique feature of this trial will be the use of Telepsychiatry to standardize observer-administered neuropsychiatric evaluations. Assessments of anxiety, quality of life, and adherence to therapy, as well as pathogenetic studies of neuropsychiatric side effects, will be conducted. Intention-to-treat analyses using random regression modeling will be employed to analyze longitudinal data on prescribed PEG-IFN-alpha and ribavirin doses. Survival analyses will be used to compare the time to the development of depression between the two arms. Effective prevention of a broad range of neuropsychiatric symptoms by citalopram has the potential to diminish PEG-IFN-alpha associated morbidity and consequently, allow a greater number of patients to complete full therapy.
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- 2008
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8. Decreased [18F]MPPF binding potential in the dorsal raphe nucleus after a single oral dose of fluoxetine: a positron-emission tomography study in healthy volunteers.
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Sibon I, Benkelfat C, Gravel P, Aznavour N, Costes N, Mzengeza S, Booij L, Baker G, Soucy JP, Zimmer L, and Descarries L
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- Administration, Oral, Adult, Autoreceptors drug effects, Autoreceptors metabolism, Brain diagnostic imaging, Brain drug effects, Double-Blind Method, Humans, Male, Piperazines, Pyridines, Receptor, Serotonin, 5-HT1A metabolism, Reference Values, Antidepressive Agents, Second-Generation pharmacology, Fluorine Radioisotopes pharmacokinetics, Fluoxetine pharmacology, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Positron-Emission Tomography, Raphe Nuclei diagnostic imaging, Raphe Nuclei drug effects, Receptor, Serotonin, 5-HT1A drug effects
- Abstract
Background: Brain serotonin-1A (5-HT(1A)) autoreceptors internalize when activated by agonist or by their endogenous ligand, serotonin. This positron-emission tomography (PET) study tested the hypothesis that 5-HT(1A) autoreceptor internalization might be indexed in vivo by a decrease in the specific binding of the 5-HT(1A) radioligand, 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1 piperazinyl]ethyl-N-2-pyridinyl-benzamide ([(18)F]MPPF), in the dorsal raphe nucleus (DRN) of healthy adult men administered a single oral dose of the selective serotonin reuptake inhibitor, fluoxetine., Methods: [(18)F]MPPF binding potential was measured in the DRN and other brain regions endowed with 5-HT(1A) receptors in eight healthy volunteers, 5 hours after the randomized, double-blind administration of fluoxetine (20 mg) or placebo., Results: In every subject, [(18)F]MPPF binding potential was decreased in the DRN only (44% +/- 22 SD), in response to fluoxetine., Conclusions: Imaging the functional state of 5-HT(1A) autoreceptors (i.e., internalization) in the human brain, using [(18)F]MPPF/PET, may represent a promising avenue for investigating the neurobiology of serotonin-related disorders and notably of major depression.
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- 2008
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9. The role of dopamine in alcohol self-administration in humans: individual differences.
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Barrett SP, Pihl RO, Benkelfat C, Brunelle C, Young SN, and Leyton M
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- Adult, Amino Acids administration & dosage, Analysis of Variance, Dopamine Agents administration & dosage, Double-Blind Method, Heart Rate drug effects, Humans, Levodopa administration & dosage, Male, Phenylalanine deficiency, Self Administration, Tyrosine deficiency, Alcohol Drinking metabolism, Alcohol Drinking psychology, Dopamine metabolism, Ethanol administration & dosage, Individuality
- Abstract
Objective: To clarify dopamine's role in alcohol self-administration in a heterogeneous sample of drinkers using acute phenylalanine/tyrosine depletion (APTD)., Methods: Sixteen men with variable drinking histories were characterized on their ethanol-induced cardiac response, a marker previously proposed to index dopamine system reactivity and vulnerability to alcohol abuse. During separate sessions participants were administered (i) a nutritionally balanced (BAL) amino acid (AA) mixture, (ii) a mixture lacking the dopamine precursors, phenylalanine and tyrosine, and (iii) APTD followed by the dopamine precursor, L-DOPA. Five hours after AA administration, participants could earn units of alcohol using a progressive ratio breakpoint task., Results: Alcohol self-administration was reduced in the APTD and APTD+L-DOPA conditions relative to the BAL condition. In both cases the changes were predicted by ethanol-induced cardiac change., Conclusions: The motivation to drink is likely regulated by more than one neurobiological mechanism. Individual differences in cardiac responsivity to ethanol might provide a peripheral marker of responsiveness to pharmacological manipulations of dopamine.
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- 2008
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10. Bright light exposure during acute tryptophan depletion prevents a lowering of mood in mildly seasonal women.
- Author
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aan het Rot M, Benkelfat C, Boivin DB, and Young SN
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- Adolescent, Adult, Amino Acids administration & dosage, Amino Acids blood, Amino Acids pharmacology, Cross-Over Studies, Double-Blind Method, Female, Humans, Light, Psychiatric Status Rating Scales, Seasonal Affective Disorder metabolism, Seasons, Sleep drug effects, Affect physiology, Phototherapy, Seasonal Affective Disorder therapy, Tryptophan deficiency
- Abstract
We investigated the influence of bright light exposure on the mood-lowering effect of acute tryptophan depletion (ATD). Mildly seasonal healthy young women without a personal or family history of psychiatric disorders remained in either dim or bright light during two test days. Tryptophan-deficient and nutritionally balanced amino acid mixtures were administered in counterbalanced order. Mood state was assessed using the Profile of Mood States (POMS) and Visual Analogue Scales (VAS). In dim light, ATD decreased POMS scores across most subscales, indicating a worsening of mood. In bright light, mood was unaffected by ATD. Thus, bright light blocked the worsening of mood caused by ATD. This was also observed on the positive mood VAS. These results indicate a direct, immediate interaction between bright light and serotonin function. Bright light might help protect against ATD-induced mood change by increasing serotonin above the threshold level below which there is a lowering of mood.
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- 2008
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11. Effect of tryptophan hydroxylase-2 gene variants on suicide risk in major depression.
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Lopez de Lara C, Brezo J, Rouleau G, Lesage A, Dumont M, Alda M, Benkelfat C, and Turecki G
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- Adolescent, Adult, Aggression psychology, Depressive Disorder, Major psychology, Family, Female, Genetic Predisposition to Disease genetics, Humans, Impulsive Behavior genetics, Impulsive Behavior psychology, Linkage Disequilibrium, Male, Pedigree, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Suicide psychology, Depressive Disorder, Major enzymology, Depressive Disorder, Major genetics, Genetic Variation, Suicide statistics & numerical data, Tryptophan Hydroxylase genetics
- Abstract
Background: Suicide and depressive disorders are strongly associated, yet not all depressed patients commit suicide. Genetic factors may partly explain this difference. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene and its 5' upstream region may predispose to suicide in major depressive disorder (MDD) and whether this predisposition is mediated by impulsive-aggressive behaviors (IABs)., Methods: We genotyped 14 single nucleotide polymorphisms (SNPs) in 259 depressed subjects, 114 of which committed suicide while depressed. Phenotypic assessments were carried out by means of proxy-based interviews. Single-marker and haplotype association analyses were conducted. Differences in behavioral and personality traits according to genotypic variation were investigated, as well as genetic and clinical predictors of suicide., Results: We found two upstream and two intronic SNPs associated with suicide. No direct effect of these variants was observed on IABs. However, a slight association with reward dependence scores was found. Controlling for suicide risk factors, two SNPs (rs4448731 and rs4641527) significantly predicted suicide, along with cluster B personality disorders and family history of suicide., Conclusions: The TPH2 gene and its 5' upstream region variants may be involved in the predisposition to suicide in MDD; however, our findings do not support the role of IABs as mediators.
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- 2007
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12. Lack of effect of acute dopamine precursor depletion in nicotine-dependent smokers.
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Casey KF, Benkelfat C, Young SN, and Leyton M
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- Adult, Dopamine Agents administration & dosage, Humans, Levodopa administration & dosage, Male, Pain Measurement methods, Phenylalanine deficiency, Self Administration, Surveys and Questionnaires, Time Factors, Tyrosine deficiency, Diet, Protein-Restricted methods, Dopamine physiology, Tobacco Use Disorder physiopathology, Tobacco Use Disorder psychology, Tobacco Use Disorder therapy
- Abstract
Rationale: Nicotine increases dopamine (DA) release but its role in nicotine dependence remains unclear., Objective: To assess the role of DA in nicotine craving and self-administration using acute phenylalanine/tyrosine depletion (APTD)., Methods: Fifteen nicotine-dependent men ingested, a minimum of 3days apart, a nutritionally balanced amino acid (AA) mixture (BAL), a mixture deficient in the catecholamine precursors, phenylalanine and tyrosine, and APTD followed by the immediate DA precursor, L-DOPA. Beginning 3h after ingestion of the AA mixture, subjects smoked 4 cigarettes. Craving, mood, and other aspects of subjective state were assessed with self-report scales. Smoking puff topography was measured with a computerized flowmeter., Results: APTD did not change smoking puff topography, cigarette craving, or subjective effects of smoking., Conclusions: The findings suggest that in nicotine-dependent smokers craving for cigarettes, subjective effects of nicotine, and the self-administration of freely available cigarettes are largely unrelated to acute changes in DA neurotransmission.
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- 2006
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13. Lack of effects on core obsessive-compulsive symptoms of tryptophan depletion during symptom provocation in remitted obsessive-compulsive disorder patients.
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Berney A, Sookman D, Leyton M, Young SN, and Benkelfat C
- Subjects
- Adult, Analysis of Variance, Double-Blind Method, Female, Humans, Male, Psychiatric Status Rating Scales, Secondary Prevention, Treatment Outcome, Tryptophan metabolism, Cognitive Behavioral Therapy methods, Obsessive-Compulsive Disorder therapy, Selective Serotonin Reuptake Inhibitors therapeutic use, Tryptophan deficiency
- Abstract
Background: Pharmacological evidence support that enhancement of serotonin (5-HT) neurotransmission is critical for treatment efficacy in obsessive-compulsive disorder (OCD). Surprisingly, acute tryptophan depletion (ATD), a procedure known to reduce 5-HT neurotransmission, carried out in remitted OCD patients on selective serotonin reuptake inhibitors (SSRIs) failed to worsen obsessive-compulsive (OC) symptoms. We hypothesized that the putative symptom exacerbation resulting from ATD would only be observed during symptom provocation but not at rest., Methods: Double-blind placebo-controlled ATD study conducted in 16 OCD patients with stable improvement under either SSRI (n = 8) or specialized cognitive behavior therapy alone (n = 8), coupled with gradual symptom provocation, performed 5 hours after drink ingestion., Results: Acute tryptophan depletion markedly reduced total and free plasma tryptophan levels but did not significantly increase obsessions or compulsions at rest or following symptom provocation. However, subjective distress in response to triggering situations was significantly higher during ATD; significant mood lowering was also present during ATD., Conclusions: These results are consistent with the view that relapses in OC core symptoms in remitted OCD patients may not depend solely on short-term changes in presynaptic 5-HT availability. In contrast to its apparent lack of effect on core OC symptoms, ATD affected the patient's mood and distress level resulting from provocation.
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- 2006
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14. alpha-[11C]Methyl-L-tryptophan trapping in the orbital and ventral medial prefrontal cortex of suicide attempters.
- Author
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Leyton M, Paquette V, Gravel P, Rosa-Neto P, Weston F, Diksic M, and Benkelfat C
- Subjects
- Adult, Brain Mapping, Depressive Disorder diagnostic imaging, Depressive Disorder psychology, Female, Humans, Image Interpretation, Computer-Assisted, Male, Positron-Emission Tomography, Psychiatric Status Rating Scales, Tryptophan pharmacokinetics, Prefrontal Cortex diagnostic imaging, Prefrontal Cortex metabolism, Radiopharmaceuticals pharmacokinetics, Suicide, Attempted psychology, Tryptophan analogs & derivatives
- Abstract
Low serotonin neurotransmission is thought to increase vulnerability to suicidal behavior. To test this hypothesis, we measured brain regional serotonin synthesis, as indexed by PET and alpha-[(11)C]methyl-L-tryptophan trapping, in 10 patients who had made a high-lethality suicide attempt and 16 healthy controls. Compared to healthy controls, suicide attempters had reduced normalized alpha-[(11)C]methyl-L-tryptophan trapping in orbital and ventromedial prefrontal cortex. alpha-[(11)C]Methyl-L-tryptophan trapping in these regions correlated negatively with suicide intent. Low serotonin synthesis in the prefrontal cortex might lower the threshold for suicidal behavior.
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- 2006
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15. STin2 variant and family history of suicide as significant predictors of suicide completion in major depression.
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Lopez de Lara C, Dumais A, Rouleau G, Lesage A, Dumont M, Chawky N, Alda M, Benkelfat C, and Turecki G
- Subjects
- Adolescent, Adult, Case-Control Studies, Chi-Square Distribution, Depressive Disorder, Major mortality, Family Health, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Pedigree, Personality genetics, Personality Tests standards, Polymorphism, Genetic genetics, Predictive Value of Tests, Quebec epidemiology, Risk Factors, Tandem Repeat Sequences genetics, Depressive Disorder, Major genetics, Gene Frequency genetics, Serotonin Plasma Membrane Transport Proteins genetics, Suicide statistics & numerical data
- Abstract
Background: Suicide is the most serious outcome of major depression, yet not all depressed patients will commit suicide. Genes, along with other factors, might account for this difference. Serotonergic alterations have been observed in suicide and depression and impulsive-aggressive behaviors. Therefore, we aimed to identify predictors of suicide, considering genetic variation at the serotonin transporter (5-HTT) gene., Methods: We investigated the 5-HTT gene-linked polymorphic region (5-HTTLPR) and intron 2 (STin2) variants of this gene and their relationship to behavioral and clinical risk factors for suicide in a sample of depressed suicides (n =106) and depressed control subjects (n =152), diagnosed by means of proxy-based interviews., Results: We found a significant association of suicide completion with having at least one copy of the STin2 10 allele [chi(2)(1) = 10.833, p = .002]. No differences were found for the 5-HTTLPR variable number of tandem repeats. After controlling for behavioral and clinical risk factors for suicide, the STin2 variant remained a significant predictor of suicide in major depression when jointly considered with a family history of suicide (odds ratio 5.560, 95% confidence interval 1.057-29.247)., Conclusions: The STin2 locus might account, at least in part, for the observed familial aggregation of suicidal behavior. These results should be further explored in families where clustering of suicidal behavior is observed.
- Published
- 2006
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16. Clinical and neurochemical effect of acute tryptophan depletion in unaffected relatives of patients with bipolar affective disorder.
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Quintin P, Benkelfat C, Launay JM, Arnulf I, Pointereau-Bellenger A, Barbault S, Alvarez JC, Varoquaux O, Perez-Diaz F, Jouvent R, and Leboyer M
- Subjects
- Acute Disease, Adult, Antidepressive Agents, Tricyclic therapeutic use, Bipolar Disorder drug therapy, Blood Platelets metabolism, Cross-Over Studies, Double-Blind Method, Female, Humans, Imipramine therapeutic use, Male, Serotonin blood, Synaptic Transmission physiology, Tryptophan blood, Bipolar Disorder genetics, Bipolar Disorder metabolism, Brain metabolism, Tryptophan deficiency
- Abstract
Background: The lowering of mood induced by an acute tryptophan depletion (ATD) has been proposed as a candidate endophenotype for the vulnerability to manic-depressive illness. This study tests this hypothesis in relatives of probands from well-characterized multiplex families affected with bipolar affective disorder (BAD)., Methods: In a double-blind, crossover design, 20 unaffected relatives (URs) and 19 control subjects received either a 100-g amino acid (AA) drink devoid of tryptophan or a placebo, respectively. Clinical and biochemical effects of ATD were compared between unaffected relatives of BAD probands and age- and sex-matched control subjects., Results: At 5 hours after AA drink ingestion, relative to the placebo, ATD resulted in 74% and 84% decreases in total plasma tryptophan concentrations in control subjects and relatives of patients with BAD, respectively. Unlike control subjects unaffected relatives experienced a lowering of mood during ATD but not with the placebo. Furthermore, URs tended to show increased impulsivity in the ATD condition. Measurements obtained before ingestion of the AA drink indicated that, relative to control subjects URs exhibited lower serotonin platelet concentrations, lower affinity, and fewer binding sites of the serotonin transporter for imipramine; these differences were unaffected by ATD., Conclusion: These results replicate and extend previous findings suggesting that URs of patients with BAD are more susceptible to low tryptophan availability. This finding may bear significance in the purported role of serotonergic mechanisms in the vulnerability to depressive syndrome and/or illness.
- Published
- 2001
- Full Text
- View/download PDF
17. Regional cerebral metabolic asymmetries replicated in an independent group of patients with panic disorders.
- Author
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Nordahl TE, Stein MB, Benkelfat C, Semple WE, Andreason P, Zametkin A, Uhde TW, and Cohen RM
- Subjects
- Adult, Antidepressive Agents, Tricyclic therapeutic use, Female, Glucose metabolism, Hippocampus diagnostic imaging, Hippocampus metabolism, Humans, Imipramine therapeutic use, Male, Panic Disorder diagnostic imaging, Panic Disorder psychology, Prefrontal Cortex diagnostic imaging, Prefrontal Cortex metabolism, Tomography, Emission-Computed, Brain Chemistry physiology, Functional Laterality physiology, Panic Disorder metabolism
- Abstract
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.
- Published
- 1998
- Full Text
- View/download PDF
18. Relapse of depression after rapid depletion of tryptophan.
- Author
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Leyton M, Young SN, and Benkelfat C
- Subjects
- Depressive Disorder psychology, Humans, Recurrence, Depressive Disorder metabolism, Tryptophan metabolism
- Published
- 1997
- Full Text
- View/download PDF
19. Serotonin and alcohol intake, abuse, and dependence: findings of animal studies.
- Author
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LeMarquand D, Pihl RO, and Benkelfat C
- Subjects
- Animals, Brain physiopathology, Dopamine physiology, Motivation, Alcohol Drinking physiopathology, Alcohol Withdrawal Delirium physiopathology, Alcoholism physiopathology, Receptors, Serotonin physiology, Serotonin physiology
- Abstract
Despite a relatively large body of literature on the role of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) in the regulation of alcohol intake, the functional significance of serotonergic neurotransmission and its relationship to alcohol intake, abuse, and dependence remains to be fully elucidated. In part two of this review, the experimental (animal) data is summarized along two lines: the effects of serotonergic manipulations on the intake of alcohol, and the effects of acute and chronic alcohol intake, as well as the withdrawal of chronic alcohol, on the serotonergic system. It is concluded that serotonin mediates ethanol intake as a part of its larger role in behavior modulation, such that increases in serotonergic functioning decrease ethanol intake, and decreased serotonergic functioning increases ethanol intake. Ethanol produces transient increases in serotonergic functioning that activate the mesolimbic dopaminergic reward system. The results are discussed in light of recent theories describing the regulatory role of serotonin in general behavior.
- Published
- 1994
- Full Text
- View/download PDF
20. Serotonin and alcohol intake, abuse, and dependence: clinical evidence.
- Author
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LeMarquand D, Pihl RO, and Benkelfat C
- Subjects
- Brain physiopathology, Humans, Synaptic Transmission physiology, Alcohol Drinking physiopathology, Alcoholism physiopathology, Serotonin physiology
- Abstract
A large body of literature has emerged concerning the role of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) in the regulation of alcohol intake and the development of alcoholism. Despite the wealth of information, the functional significance of this neurotransmitter remains to be fully elucidated. This paper, part one of a two-part review, summarizes the available clinical research along two lines: the effects of alcohol on serotonergic functioning and the effects of pharmacological manipulation of serotonergic functioning on alcohol intake in normal (nonalcohol dependent) and alcohol-dependent individuals. It is concluded that considerable evidence exists to support the notion that some alcoholic individuals may have lowered central serotonin neurotransmission.
- Published
- 1994
- Full Text
- View/download PDF
21. Serum antibody for somatostatin-14 and prodynorphin 209-240 in patients with obsessive-compulsive disorder, schizophrenia, Alzheimer's disease, multiple sclerosis, and advanced HIV infection.
- Author
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Roy BF, Benkelfat C, Hill JL, Pierce PF, Dauphin MM, Kelly TM, Sunderland T, Weinberger DR, and Breslin N
- Subjects
- Adult, Antibodies immunology, Antibody Formation immunology, Autoimmunity, Binding, Competitive, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Alzheimer Disease immunology, Antibodies blood, Enkephalins immunology, HIV Seropositivity immunology, Multiple Sclerosis immunology, Obsessive-Compulsive Disorder immunology, Protein Precursors immunology, Schizophrenia immunology, Somatostatin immunology
- Abstract
Patients with obsessive-compulsive disorder (OCD) demonstrated significant levels of antibody for somatostatin-28, its C-terminal fragment somatostatin-14, and prodynorphin. In contrast there were lower levels of reactivity for somatostatin-28(1-14) (the N-terminal fragment of somatostatin-28) and negligible reactivity for several other peptides including beta-endorphin and corticotropin. Healthy volunteers and disease controls [schizophrenia, Alzheimer's disease, multiple sclerosis, and subjects with advanced human immunodeficiency virus (HIV) infection] exhibited negligible reactivity. These data raise the consideration of an autoimmune mechanism for some OCD.
- Published
- 1994
- Full Text
- View/download PDF
22. Lack of correlation between plasma DOPEG and urinary MOPEG levels in depressed patients.
- Author
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Lôo H, Dennis T, Vanelle JM, Rouquier L, Poirier-Littré MF, Garreau M, Benkelfat C, Sechter D, and Scatton B
- Subjects
- Adult, Age Factors, Aged, Anti-Anxiety Agents therapeutic use, Benzodiazepines, Depressive Disorder drug therapy, Female, Humans, Male, Methoxyhydroxyphenylglycol analogs & derivatives, Middle Aged, Opium therapeutic use, Sex Factors, Depressive Disorder metabolism, Glycols blood, Glycols urine, Methoxyhydroxyphenylglycol blood, Methoxyhydroxyphenylglycol urine
- Abstract
Twenty-four-hour urinary excretion of 3-methoxy,4-hydroxyphenylethyleneglycol (MOPEG) and levels of free and conjugated plasma 3,4-dihydroxyphenylethyleneglycol (DOPEG) were measured in 56 depressed patients to find a possible correlation between these two peripheral indices of cerebral noradrenergic activity. Plasma DOPEG was measured at 9:00 AM on the same day that urine was collected for the measurement of MOPEG. All depressed patients were diagnosed as having affective disorders according to DSM-III. No correlation was found between plasma free or conjugated DOPEG levels and urinary MOPEG output. This lack of correlation was found in the total sample of depressed patients (56), in 45 patients diagnosed as having major depressive episodes, and in 24 depressed patients diagnosed as major depressive with melancholia. The authors discuss the significance of this lack of correlation between two peripheral indices of central noradrenergic metabolism.
- Published
- 1986
- Full Text
- View/download PDF
23. Changes in [3H]5-HT uptake and [3H]imipramine binding in platelets after chlorimipramine in healthy volunteers. Comparison with maprotiline and amineptine.
- Author
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Poirier MF, Galzin AM, Loo H, Pimoule C, Segonzac A, Benkelfat C, Sechter D, Zarifian E, Schoemaker H, and Langer SZ
- Subjects
- Adult, Blood Platelets metabolism, Dibenzocycloheptenes pharmacology, Female, Humans, Kinetics, Male, Maprotiline pharmacology, Middle Aged, Receptors, Neurotransmitter drug effects, Blood Platelets drug effects, Carrier Proteins, Clomipramine pharmacology, Imipramine blood, Receptors, Drug, Serotonin blood
- Abstract
In the platelets of normal healthy volunteers (n = 8) taking chlorimipramine (50 mg/day) for 1 week, the saturable uptake of [3H]5-hydroxytryptamine (5-HT) was fully inhibited at the end of the week, but returned to control values after 2 weeks washout. The Bmax of [3H]imipramine binding was decreased by 63% at the end of the treatment and remained significantly decreased below control values after 1 week washout, whereas the Kd values were increased at the end of the treatment, but had returned to baseline values after 1 week washout. The time course of recovery following the administration of chlorimipramine showed some variation between subjects, but it was necessary to wait up to 4 weeks of washout before the Bmax of [3H]imipramine returned to baseline levels. In contrast, neither 1-week treatment with maprotiline (50 mg/day) nor with amineptine (100 mg/day) changed the parameters of [3H]5-HT uptake or [3H]imipramine binding in platelets from healthy volunteers. These results support the following conclusions. (1) [3H]Imipramine binding in platelets can be down-regulated by relatively low, subtherapeutic doses of chlorimipramine. (2) It is possible to dissociate [3H]imipramine binding parameters from [3H]5-HT uptake because the time course of recovery was clearly different, indicating that [3H]imipramine labels a site linked with, but different from, the 5-HT recognition site in the transporter complex. (3) A washout of antidepressants of 4 weeks may be needed when studying the parameters of [3H]imipramine binding in platelets from depressed patients if the previous medication involved chlorimipramine. For antidepressants like maprotiline or amineptine, that act through mechanisms other than inhibition of 5-HT uptake, the time of washout appears to be less critical, although it is not possible to rule out the existence of some secondary modifications influencing the 5-HT transporter complex.
- Published
- 1987
- Full Text
- View/download PDF
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