Persistent Organic Pollutants in albacore tuna (Thunnus alalunga) from Reunion Island (Southwest Indian Ocean) and South Africa in relation to biological and trophic characteristics.

The contamination of albacore tuna (Thunnus alalunga) by Persistent Organic Pollutants (POPs), namely polychlorinated biphenyls (PCBs) and dichlorodiphenyl-trichloroethane (DDT), was investigated in individuals collected from Reunion Island (RI) and South Africa's (SA) southern coastlines in 2013, in relation to biological parameters and feeding ecology. The results showed lower PCB and DDT concentrations than those previously reported in various tuna species worldwide. A predominance of DDTs over PCBs was revealed, reflecting continuing inputs of DDT. Tuna collected from SA exhibited higher contamination levels than those from RI, related to higher dietary inputs and higher total lipid content. Greater variability in contamination levels and profiles was identified in tuna from RI, explained by a higher diversity of prey and more individualistic foraging behaviour. PCB and DDT contamination levels and profiles varied significantly in tuna from the two investigated areas, probably reflecting exposure to different sources of contamination.

Basal plasma leptin levels in healthy elderly males are related to physical fitness without impact on bone metabolism.

AIM: Investigated the relationship between leptin levels or bone remodelling and physical fitness level in healthy elderly participants. METHODS: Twenty women and 18 men (mean age 72.7 years, range 59-90) performed a maximal incremental exercise test to evaluate their maximal oxygen uptake (VOmax). Basal blood concentrations of bone biochemical markers (BM) and leptin were analysed. RESULTS: Women presented higher values of leptin than men (+34.7%, P=0.024), but no difference related to gender was observed for the other biological parameters. Leptin levels were positively correlated with Body Mass Index (BMI) in both genders. Whether adjusted or not for BMI, leptin was negatively correlated with VOmax only in men (r=-0.55, P=0.02 and r=-0.57, P=0.01, respectively). No relationship between VOmax or leptin and BM was observed, except for leptin and osteocalcin in men (r=-0.66, P=0.015). CONCLUSION: Our data suggest that neither physical fitness nor leptin level seems to have a noticeable effect in the regulation of bone cell activity in healthy elderly participants. In this specific population, physical fitness plays a crucial role on leptin secretion, independently of BMI variation, and this action appears to be sex-dependent.

Amisulpride improves depressive symptoms in acute exacerbations of schizophrenia: comparison with haloperidol and risperidone.

The Brief Psychiatric Rating Scale (BPRS) anxiety/depression subscore has been used to assess affective symptoms in three studies (n = 612) comparing amisulpride (400-800 mg/day, n = 339) with haloperidol (15-20 mg/day, n = 160) and risperidone (8 mg/day, n = 113) in the treatment of acute exacerbations of schizophrenia. At endpoint, the mean improvement in the anxiety/depression subscore showed a significant (P = 0.011) difference in favour of amisulpride (5.6+/-6.1) compared with haloperidol (4.4+/-5.5) and risperidone (3.7+/-4.7). Amisulpride provided a significantly greater improvement compared both to haloperidol and risperidone in more severely depressed patients (BPRS anxiety/depression subscore > or = 16 at baseline, P = 0.001). This significant advantage in favour of amisulpride is seen from the 2nd week of treatment.

Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects.

AIMS: Itraconazole is a potent inhibitor of CYP3A4 activity and is often used in combination with corticosteroids. Since the latter are partly metabolized by CYP3A4, we studied the interaction between itraconazole, prednisone and methylprednisolone in healthy male subjects. METHODS: The effects of 4 days administration of oral itraconazole (400 mg on the first day then 200 mg day-1 for 3 days) on the pharmacokinetics of prednisolone after a single oral dose of prednisone (60 mg) and the pharmacokinetics of methylprednisolone after single oral dose of methylprednisolone (48 mg) were studied in 14 healthy male subjects in a two-period cross-over trial. Plasma cortisol concentrations were determined as a pharmacodynamic index. RESULTS: Itraconazole increased the mean area under the methylprednisolone concentration-time curve from 2773 ng ml-1 h to 7011 ng ml-1 h (P < 0.001) and the elimination half-life from 3.2 h to 5.5 h (P < 0.001). The pharmacokinetics of prednisolone were unchanged. Cortisol concentrations at 24 h were lower after administration of methylprednisolone with itraconazole than after methylprednisolone alone (24 ng ml-1 vs 109 ng ml-1, P < 0.001). CONCLUSIONS: Itraconazole increased methylprednisolone concentrations markedly with enhanced suppression of endogenous cortisol secretion, but had no effect on prednisolone pharmacokinetics. The pharmacokinetic interaction between methylprednisolone and itraconazole is probably related to inhibition of hepatic CYP3A4 activity by itraconazole.

Evidence that ranolazine behaves as a weak beta1- and beta2-adrenoceptor antagonist in the rat [correction of cat] cardiovascular system.

The clinical anti-anginal effectiveness of ranolazine is currently being evaluated. However, the mechanism of its anti-ischaemic action is still unclear. The aim of this work was to establish whether ranolazine exerts functional beta-adrenoceptor antagonist activity in the rat cardiovascular system. Radioligand binding studies were performed in rat hearts and guinea-pig lungs for beta1- and beta2-adrenoceptor affinity, respectively. Ranolazine had micromolar affinity for both beta,- and beta2-adrenoceptors (pKi5.8 and 6.3, respectively). Developed tension was measured in isolated rat left atria (electrically driven at 4 Hz) and cumulative concentration/response curves to (+/-)isoprenaline (0.01-1,000 nM) constructed. Ranolazine (0.32-10 microM) surmountably but weakly antagonised isoprenaline-induced positive inotropic responses, with an apparent pA2 of 5.85 (5.69-6.00) and a slope of -0.74 (-0.70 to -0.77). In bivagotomised, atropinised pithed rats, ranolazine per se evoked marked bradycardia at doses above 10 mg/kg i.v. (maximum variation at 80 mg/kg -125+/-15 bpm, n=6, P<0.001) by a mechanism apparently unrelated to blockade of beta1- or beta2-adrenoceptors. Cumulative incremental doses of (+/-)isoprenaline (0.63 ng/kg to 0.16 mg/kg i.v.) administered to pithed rats induced concomitant depressor and chronotropic responses. Animals received either vehicle (saline 0.9% i.v., n=12), atenolol (0.04-2.5 mg/kg i.v., n=6 per dose), ICI 118551 (0.01-0.63 mg/kg i.v., n=6 or 7 per dose), (+/-)propranolol (0.01-0.63 mg/kg i.v., n=6 per dose) or ranolazine (2.5-80 mg/kg i.v., n=6 or 7 per dose) 10 min prior to isoprenaline. Ranolazine dose-dependently and competitively antagonised isoprenaline-induced decreases in diastolic arterial pressure (DAP, dose ratio 12.2 with 80 mg/kg ranolazine) and increases in heart rate (HR, dose ratio 20.3 with 80 mg/kg ranolazine). Collectively, these results demonstrate that ranolazine behaves as a weak beta1- and beta2-adrenoceptor antagonist in the rat cardiovascular system.

TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome.

Velo-cardio-facial syndrome (VCFS)/DiGeorge syndrome (DGS) is a human disorder characterized by a number of phenotypic features including cardiovascular defects. Most VCFS/DGS patients are hemizygous for a 1.5-3.0 Mb region of 22q11. To investigate the etiology of this disorder, we used a cre-loxP strategy to generate mice that are hemizygous for a 1.5 Mb deletion corresponding to that on 22q11. These mice exhibit significant perinatal lethality and have conotruncal and parathyroid defects. The conotruncal defects can be partially rescued by a human BAC containing the TBX1 gene. Mice heterozygous for a null mutation in Tbx1 develop conotruncal defects. These results together with the expression patterns of Tbx1 suggest a major role for this gene in the molecular etiology of VCFS/DGS.

Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone.

OBJECTIVE: To assess, in depressed patients, the clinical benefit of mianserin augmentation of fluoxetine or the the benefit of switching treatment from fluoxetine to mianserin. METHOD: In a 6-week double-blind study we compared the therapeutic efficiency and tolerance of mianserin 60 mg/day (N = 34), mianserin 60 mg/day plus fluoxetine 20 mg/day (N = 32) and continuing fluoxetine 20 mg/day (N = 38) in patients with major depression who did not respond to previous fluoxetine treatment. RESULTS: Intent-to-treat analysis showed that at week 6 the decrease in the Hamilton Depression rating scale score was significantly (P < or = 0.03) greater in the mianserin plus fluoxetine group when compared to the fluoxetine group (effect size 0.665). Switching from fluoxetine to mianserin gave intermediate results. Mianserin augmentation of fluoxetine was well tolerated. CONCLUSION: Mianserin augmentation of fluoxetine in patients non-responders to fluoxetine 20 mg/day increases response to treatment and is well tolerated.

Normal cardiovascular development in mice deficient for 16 genes in 550 kb of the velocardiofacial/DiGeorge syndrome region.

Hemizygous interstitial deletions in human chromosome 22q11 are associated with velocardiofacial syndrome and DiGeorge syndrome and lead to multiple congenital abnormalities, including cardiovascular defects. The gene(s) responsible for these disorders is thought to reside in a 1.5-Mb region of 22q11 in which 27 genes have been identified. We have used Cre-mediated recombination of LoxP sites in embryonic stem cells and mice to generate a 550-kb deletion encompassing 16 of these genes in the corresponding region on mouse chromosome 16. Mice heterozygous for this deletion are normal and do not exhibit cardiovascular abnormalities. Because mice with a larger deletion on mouse chromosome 16 do have heart defects, the results allow us to exclude these 16 genes as being solely, or in combination among themselves, responsible for the cardiovascular abnormalities in velocardiofacial/DiGeorge syndrome. We also generated mice with a duplication of the 16 genes that may help dissect the genetic basis of "cat eye" and derivative 22 syndromes that are characterized by extra copies of portions of 22q11, including these 16 genes. We also describe a strategy for selecting cell lines with defined chromosomal rearrangements. The method is based on reconstitution of a dominant selection marker after Cre-mediated recombination of LoxP sites. Therefore it should be widely applicable to many cell lines.

Serotonin and tolerance to delay of reward in rats.

RATIONALE: Tolerance to delay of gratification, taken to reflect impulsiveness, has been proposed to be under the preferential control of central serotonin (5-HT) processes. OBJECTIVE: The present study further examined the effects of drugs which directly or indirectly alter 5-HT transmission, on behaviour controlled by a delayed positive reinforcer. METHODS: Rats were given the choice in a T-maze between two magnitudes of reward: small (two food pellets) and immediate versus large (ten pellets) but delayed. When a 15-s waiting period was imposed in the arm leading to the large reward, rats selected this arm on 65-70% of the trials. This frequency was reduced to less than 40% when the large reward was delayed by 25 s. RESULTS: In rats whose ascending 5-HT pathways had been lesioned by infusion of 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal raphe, the introduction of the 15-s delay contingency resulted in a transient larger reduction of the frequency of choice of the now-delayed reward, compared to sham operated controls. In contrast, choice behaviour of rats given 5,7-DHT into the substantia nigra did not differ from controls. para-Chlorophenylalanine (pCPA, 150 mg/kg IP, daily for 3 days), a 5-HT synthesis inhibitor, bretazenil (0.5-8 mg/kg IP), a benzodiazepine (BZD) receptor partial agonist, and muscimol (0.25-1 mg/kg IP), a GABA(A) receptor agonist, induced a shift toward immediate reward. In contrast to the other BZDs, alprazolam (1-2 mg/kg IP) enhanced the frequency of choice of the large-but-25 s-delayed reward. Similar increased preference for the large-but-delayed reward was induced by the selective 5-HT reuptake inhibitors, fluoxetine (4-8 mg/kg IP) and fluvoxamine (4 mg/kg IP). The full 5-HT(1A) receptor agonist, 8-OH-DPAT (0.015-0.5 mg/kg IP) enhanced the frequency of choice of the large reward delayed by 25 s, whereas the partial agonists, buspirone (1-4 mg/kg IP), ipsapirone (0.5-1 mg/kg IP) and MDL 73005EF (1-2 mg/kg SC), and the antagonist, WAY 100635 (4 mg/kg SC), reduced the number of choices of the large reward delayed by 15 s. Unexpectedly, WAY 100635 (2 mg/kg), which had no effect on choice whatever the delay, did not counteract the increased tolerance to delay induced by 8-OH-DPAT (0.06 mg/kg) and further reduced the frequency of choice of the large-but- 15 s-delayed reward induced by ipsapirone (0.5 mg/kg). CONCLUSIONS: These effects on tolerance to delay may be accounted for by a subtle balance between the opposing functional consequences of pre- versus post-synaptic 5-HT(1A) receptor activation or blockade. Overall, the present results provide further support to the idea that 5-HT processes participate in the control of impulsive-related behaviour, as assessed from tolerance to delay of reward in this particular T-maze procedure.

Agreement between 'time-blind' and 'time-non-blind' assessments of depressive symptomatology.

In a 4-week study, two methods were used simultaneously in the assessment of depressive symptomatology with videotaped structured clinical interviews: a 'time-non-blind' (TNB) method (chronological order, observer aware of the previous duration of drug treatment) and a 'time-blind' (TB) method (no chronological order, rater unaware of the previous duration of treatment). Sixty newly admitted depressed inpatients with Montgomery-Asberg Depression Rating Scale scores higher than 20 were assessed before (D0), after 10 days (D10) and after 28 days (D28) of antidepressant treatment. Agreement between TNB and TB methods on the Montgomery-Asberg Depression Rating Scale, measured by intra-class correlation coefficients, was good at D0 (0.68), excellent at D10 (0.81) and D28 (0.86), but not significantly different between D0, D10 and D28. The statistical method of Bland and Altman (1986) was also used to evaluate the degree of agreement. Results of this second analysis were in accordance with the intra-class correlation coefficient results, and showed significantly (P < 0.05) higher D0-D28 and D10-D28 intrasubject changes with the TB method, which were largely accounted for by some particular items (inner tension, pessimism, lassitude). With the Clinical Global Impression-Severity score, the Bland and Altman method failed to show significant differences between the two methods, and compared with the Montgomery-Asberg Depression Rating Scale, intra-class correlation coefficients were lower with larger confidence intervals, suggesting that global ratings are less reliable than itemized symptom ratings.

Goosecoid-like (Gscl), a candidate gene for velocardiofacial syndrome, is not essential for normal mouse development.

Velocardiofacial syndrome (VCFS) and DiGeorge syndrome (DGS) are characterized by a wide spectrum of abnormalities, including conotruncal heart defects, velopharyngeal insufficiency, craniofacial anomalies and learning disabilities. In addition, numerous other clinical features have been described, including frequent psychiatric illness. Hemizygosity for a 1.5-3 Mb region of chromosome 22q11 has been detected in >80% of VCFS/DGS patients. It is thought that a developmental field defect is responsible for many of the abnormalities seen in these patients and that the defect occurs due to reduced levels of a gene product active in early embryonic development. Goosecoid-like ( GSCL ) is a homeobox gene which is present in the VCFS/DGS commonly deleted region. The mouse homolog, Gscl, is expressed in mouse embryos as early as E8.5. Gscl is related to Goosecoid ( Gsc ), a gene required for proper craniofacial development in mice. GSCL has been considered an excellent candidate for contributing to the developmental defects in VCFS/DGS patients. To investigate the role of Goosecoid-like in VCFS/DGS etiology, we disrupted the Gscl gene in mouse embryonic stem cells and produced mice that transmit the disrupted allele. Mice that are homozygous for the disrupted allele appear to be normal and they do not exhibit any of the anatomical abnormalities seen in VCFS/DGS patients. RNA in situ hybridization to mouse embryo sections revealed that Gscl is expressed at E8.5 in the rostral region of the foregut and at E11.5 and E12.5 in the developing brain, in the pons region and in the choroid plexus of the fourth ventricle. Although the gene inactivation experiments indicate that haploinsufficiency for GSCL is unlikely to be the sole cause of the developmental field defect thought to be responsible for many of the abnormalities in VCFS/DGS patients, its localized expression during development could suggest that hemizygosity for GSCL, in combination with hemizygosity for other genes in 22q11, contributes to some of the developmental defects as well as the behavioral anomalies seen in these patients. The mice generated in this study should help in evaluating these possibilities.

Isolation and characterization of a human gene containing a nuclear localization signal from the critical region for velo-cardio-facial syndrome on 22q11.

Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome are congenital disorders characterized by craniofacial anomalies, conotruncal heart defects, immune deficiencies, and learning disabilities. Both diseases are associated with similar hemizygous 22q11 deletions, indicating that haploinsufficiency of a gene(s) in 22q11 is responsible for their etiology. We describe here a new gene called NLVCF, which maps to the critical region for VCFS on 22q11 between the genes HIRA and UFD1L. NLVCF encodes a putative protein of 206 amino acids. The coding region encompasses four exons that span a genomic interval of 3.4 kb. Coding sequence analysis revealed that NLVCF is a novel gene that contains two consensus sequences for nuclear localization signals. The Nlvcf mouse homolog is 75% identical in amino acid sequence and maps to the orthologous region on mouse chromosome 16. The human NLVCF transcript is 1.3 kb in size and is expressed at varying levels in many fetal and adult tissues. Whole-mount in situ hybridization showed that Nlvcf is expressed in most structures of 9.5-dpc mouse embryos, with especially high expression in the head as well as in the first and second pharyngeal arches. NLVCF and HIRA are divergently transcribed, and their start codons lie approximately 1 kb apart in both humans and mice. Interestingly, the two genes exhibit a similar expression pattern in mouse embryos, suggesting that they may share common regulatory elements. The pattern of expression of NLVCF and its localization in the critical region suggest that NLVCF may contribute to the etiology of VCFS.

Anhedonia and relapse in alcoholism.

The aim of this study was to determine the role of anhedonia among other psychopathological dimensions in the relapse of alcoholics 6 months after withdrawal. Psychometric assessments included: the Social and Physical Anhedonia Scales, the Sensation Seeking Scale, the Pleasure-Displeasure Scale (including Fawcett-Clark's Pleasure Scale), the Depressive Mood Scale, the Thymasthenic Syndrome Rating Scale and the Comprehensive Psychopathological Rating Scale. Forty-four alcoholics participated in the study. The baseline values recorded during the second week of treatment showed that the more anhedonic the alcoholics were, the less they sought sensations. Type 2 alcoholics (Cloninger's classification) scored higher on the Thrill and Adventure Seeking Subscale. Relapsed alcoholics had higher baseline values on the Thrill and Adventure Seeking Subscale. This was in agreement with the step-wise discriminant analysis which showed that this subscale was the main variable that differentiated abstinent alcoholics from those who relapsed. Our results indicate that anhedonia does not predict relapse.

Amisulpride, and atypical antipsychotic, in the treatment of acute episodes of schizophrenia: a dose-ranging study vs. haloperidol. The Amisulpride Study Group.

This 4-week, double-blind, randomized study was undertaken to determine the dose-response relationship of amisulpride in 319 patients with acute exacerbation of schizophrenia. Fixed doses of amisulpride (400, 800 and 1200 mg/day) and haloperidol (16 mg/day) were compared to amisulpride, 100 mg/day, as a potentially subtherapeutic dose. Efficacy data (BPRS total score and PANSS positive subscale) in the amisulpride groups generated a bell-shaped dose-response curve, with 400 mg/day and 800 mg/day being the most effective treatments for positive symptoms. Parkinsonism did not increase significantly between baseline and endpoint with amisulpride 400, 800 and 1200 mg/day compared to the amisulpride 100 mg/day group, whereas the difference was significant for haloperidol (P<0.05). It is concluded that amisulpride 400 mg and 800 mg/day is highly effective in treating the positive symptoms of schizophrenia, with less extrapyramidal side-effects than haloperidol 16 mg/day.

Blunted 5-HT1A-receptor agonist-induced corticotropin and cortisol responses after long-term ipsapirone and fluoxetine administration to healthy subjects.

OBJECTIVES: To assess whether acute 5-hydroxytryptamine-1A (5-HT1A)-receptor-mediated corticotropin, cortisol, and temperature responses are maintained after 3 weeks of treatment with controlled-release (CR) ipsapirone and fluoxetine compared with placebo and whether changes are reversible after cessation of treatment. METHODS: This was a randomized parallel-group study. Ten healthy subjects received ipsapirone CR or fluoxetine, and eight received placebo in a double-blind manner. An ipsapirone challenge test with 20 mg ipsapirone immediate-release formulation (IR) was performed before treatment (day 0) and after 20 days of treatment with placebo, 80 mg/day ipsapirone CR, or 20 mg/day fluoxetine (day 21). From day 22 to day 34 all subjects received placebo in a simple-blind manner. A third ipsapirone challenge test was performed on day 35. RESULTS: Before treatment, resting plasma corticotropin and cortisol concentrations and increases in plasma corticotropin and cortisol concentrations after challenge with 20 mg ipsapirone IR were similar for the three groups. After 20 days of treatment, plasma corticotropin and cortisol concentrations were similar before challenge, but ipsapirone IR-induced increases in plasma corticotropin and cortisol concentrations were significantly lower in both the ipsapirone CR group (corticotropin, 6.5 +/- 2 pg/ml; cortisol, 1.5 +/- 0.7 micrograms/dl) and fluoxetine group (corticotropin 4.4 +/- 2 pg/ml; cortisol 1.5 +/- 0.7 micrograms/dl) compared with placebo (corticotropin, 34 +/- 14 pg/ml; cortisol, 5.8 +/- 2 micrograms/dl, mean +/- SEM). After 2 weeks of placebo administration, plasma corticotropin and cortisol responses to ipsapirone IR again became identical in all three groups. Plasma ipsapirone concentrations were similar in all groups during each challenge. The hypothermic response to ipsapirone IR showed no difference before treatment, at the end of the treatment period, or 2 weeks after cessation of treatment. Long-term administration of antidepressants to the healthy subjects did not lead to any serious adverse effects. CONCLUSIONS: Long-term administration of fluoxetine and ipsapirone did not influence resting plasma corticotropin and cortisol concentrations in the morning. Stimulation of corticotropin and cortisol release by a selective 5-HT1A-agonist is reduced with long-term administration of these serotoninergic antidepressants. This subsensitivity of postsynaptic 5-HT1A-receptors is reversible.

Involvement of central cannabinoid (CB1) receptors in the establishment of place conditioning in rats.

The involvement of cannabinoid processes in positive reinforcement was studied using an unbiased, one-compartment, conditioned place preference (CPP) procedure in rats. This was achieved by examining the ability of the selective antagonist of the CB1 cannabinoid receptor subtype, SR 141716, to counteract the CPP supported by classical reinforcers. The acquisition of CPP induced by cocaine (2 mg/kg), morphine (4 mg/kg) and food (standard chow and sucrose pellets) was dose-dependently blocked by pre-pairing administration of SR 141716 (0.03-3 mg/kg). However, SR 141716 (up to 10 mg/kg) did not significantly counteract the expression of cocaine-induced CPP. On the other hand, the synthetic CB receptor agonist, WIN 55212-2 (0.3-1 mg/kg), established a robust place aversion (CPA), as already described with other agonists, and CPP was never observed, even at 100-fold lower doses. The aversive effect of WIN 55212-2 was reversed by SR 141716 (0.3-1 mg/kg), suggesting that it was accounted for by the stimulation of CB1 receptors. These findings indicate that, on their own, CB receptor agonists are unable to generate the processes necessary to induce a pleasurable state in animals, as assessed in place conditioning procedures. Nevertheless, a cannabinoid link may be involved in the neurobiological events, allowing the perception of the rewarding value of various kinds of reinforcers. However, a permanent endogenous cannabinoid tone seems unlikely to be necessary to ensure the organism a basal hedonic level since, given alone, SR 141716 supported neither CPP nor CPA.

Whole blood serotonin content, tryptophan concentrations, and impulsivity in anorexia nervosa.

BACKGROUND: We hypothesized that anorectics with or without bulimic features would differ on impulsivity and indices of central serotoninergic function (high impulsivity being correlated with reduced serotoninergic function). METHODS: For all patients impulsivity rating scales and questionnaires detailing severity of eating disorder were assessed, and whole blood serotonin concentration (5-HT), free and total tryptophan (TT) concentrations, and large neutral amino acids (LNAA) were assayed. RESULTS: Nineteen patients with anorexia nervosa were included, 10 presented associated bulimic features and nine did not. Twelve healthy matched controls were also included. Our hypothesis was not verified. However, tryptophan concentration and the ratio of tryptophan concentration to LNAA allow us to separate controls from anorectics, whereas 5-HT concentration does not. Two significant and positive correlations were found: between impulsivity and anxiety in the total anorectic population, and between anxiety and serotonin in the impulsive group. CONCLUSIONS: All measured peripheral biologic indices except 5-HT concentration may be of interest in this pathology. Impulsivity and anxiety seem to be two personality components involved in anorexia nervosa. This study lead us to the necessity of redefining impulsivity in anorexia nervosa.

Rating antidepressant efficacy with naturalistic live versus structured videotaped interviews.

Two different methods were compared in the assessment of depressive symptomatology improvement: live naturalistic (N) performed by the patient's therapist, and from videotape record of structured clinical interview (VSI) assessed by an independent rater out of five psychiatrists. Sixty-one newly admitted depressed inpatients, with a Montgomery and Asberg Depression Rating Scale (MADRS) total score above 20, were assessed before antidepressant treatment (DO), after 10 days (D10) and 4 weeks of treatment (D28). Assessments were based on the MADRS and the Depression Retardation Rating Scale (DRRS) for both N and VSI methods, and on the SCL-90-R for self-rating. With the MADRS, the N method was shown to be more sensitive to symptomatology change than the VSI method, but the VSI method was more correlated to self-assessment than the N method was. However, these results were not replicated on the DRRS, for which an underscoring with the VSI method was evidenced as compared to the N method. As shown in other studies, the poorest agreement between the two methods was evidenced at DO, suggesting a "novelty effect" particularly with the VSI method. This "novelty effect" may be all the more pronounced if a personality disorder is associated to depression. Consequently, information concerning each patient before rating videotapes is needed, as well as investigations in the field of depression and personality disorders. The greater change observed in MADRS with the N method as compared to the VSI method, may be due non-specific factors related mostly to therapist expectations by comparison to neutral raters. This hypothesis should be tested in the placebo group of a double-blind study, and, if confirmed, the use of VSI methods, by minimising non-specific factors of improvement due to therapist expectations, may decrease the placebo response in antidepressant drug trials.

Measures of anhedonia and hedonic responses to sucrose in depressive and schizophrenic patients in comparison with healthy subjects.

Anhedonia may be considered as a transnosological feature of depression and schizophrenia. The aim of the present study was to assess hedonic responses to sucrose solutions and sweet taste perception threshold in patients with major depression and in schizophrenic patients in comparison with healthy subjects (matched for age and gender with depressive patients), and to compare these responses to evaluations by the Physical and Social Anhedonia scale of Chapman and the Pleasure Scale of Fawcett, generally used to quantify anhedonia. Hedonic responses to sucrose solutions were similar in patients with major depression (n = 20), schizophrenia (n = 20), and healthy controls (n = 20). Sweet taste perception threshold was significantly higher in depressive patients than in controls. Hedonic response to sucrose was inversely correlated with physical Anhedonia Scores and sweet taste perception threshold with Pleasure Scale scores. Measures of hedonia/anhedonia were not related with the intensity of depression or anxiety as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Scale, respectively. In 11 depressed patients hospitalised for 17 to 33 days, neither hedonic ratings to sucrose solutions, sweet taste perception threshold, Physical, Social Anhedonia scores nor Pleasure Scale scores were modified in spite of substantial decrease in MADRS or Hamilton Anxiety scores. Hedonic responses to sucrose solutions and sweet taste perception threshold may be used as complementary evaluation to quantify anhedonia.

The dopamine D2 receptor gene TaqI A polymorphism is not associated with Novelty Seeking, Harm Avoidance and Reward Dependence in healthy subjects.

Allele A1 of the TaqI A restriction fragment length polymorphism (RFLP) of the dopamine D2 receptor gene has been found to be associated with substance abuse and alcoholism. The personality trait of Novelty Seeking (NS) is also associated with substance abuse and dependence. We hypothesised, on the basis of involvement of dopaminergic mechanisms in substance abuse, that the presence of allele A1 of the dopamine D2 receptor gene may represent a genetic predisposition for the NS personality trait. We investigated, therefore, whether the allele A1 of the TaqI A RFLP of the dopamine D2 receptor gene is associated with the NS dimension of the Tridimensional Personality Questionnaire (TPQ) in healthy Caucasian subjects with no history of alcohol or substance abuse or dependence. We genotyped 204 subjects aged 18 to 30 years. There was no association between any of the alleles of the D2 receptor genes and any of the TPQ scores (NS, Harm Avoidance, Reward Dependence). We conclude that allele A1 of the TaqI A RFLP of the dopamine D2 receptor is not associated with NS personality trait in healthy Caucasian subjects.