Psychiatric diagnoses and personality traits associated with disadvantageous decision-making.

OBJECTIVE: Decision-making impairment is an important feature of psychiatric disorders. In a large comorbid psychiatric population, we explored the link between decision-making deficit and clinical variables. METHOD: We used the Iowa Gambling Task to measure decision-making in 317 patients. Psychiatric diagnoses were made according to the DSM-IV criteria. Self-questionnaires were used to assess several personality traits. The last and most severe suicidal acts were characterized. RESULTS: (1) After controlling for age and medication intake, a past history of suicide attempt (OR=2.0 [1.1-3.8]) and normothymic bipolar disorders (OR=3.4 [1.1-10.5]) were significantly and independently associated with impaired decision-making. (2) Decision-making performance was significantly correlated with affective lability. (3) No association was found between decision-making skills and suicidal characteristics. DISCUSSION: A lack of statistical power may have masked associations with obsessive-compulsive disorder and anorexia nervosa. We did not control for other cognitive functions except attention. CONCLUSION: This study supports the independent association of decision-making impairment with vulnerability to suicidal behaviour but not with substance abuse. Normothymic bipolar disorders, but not unipolar disorders, were also linked to low performance. At the dimensional level, impulsivity and decision-making abilities may be distinct processes. Affective regulation skills appear to be a major influence on decision-making performance and following a relevant therapeutic target.

Association between violent suicidal behavior and the low activity allele of the serotonin transporter gene.

There is compelling evidence that serotonin system dysfunction is associated with certain behavioral disorders, such as suicidal behavior and impulsive aggression. A functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) was recently identified and the presence of the short allele found to be associated with a lower level of expression of the gene, lower levels of 5-HT uptake, suicidal behavior and anxiety-related traits. We genotyped 51 West European Caucasians who had made violent suicide attempts and 139 controls of the same ethnic origin, with no history of suicidal behavior. The frequencies of the S allele and the SS genotype were significantly higher in the violent suicide attempters than in the controls. The odds ratio for the SS genotype vs the LL genotype was 3.63 (95% CI (1.27--10.40)). This suggests that a change in expression of the gene encoding the 5-HT transporter may be involved in violent suicidal behavior.

[Abuse of and dependence on zolpidem: a report of seven cases]. / Abus et dépendance au zolpidem: à propos de sept cas.

Zolpidem is an hypnotic drug that belongs to the imidazopyridine family. Its chemical structure is different from that of benzodiazepines though both type of drugs bind specifically to the same site of the GABA-A macromolecular complex: the omega 1 benzodiazepine receptor. This mechanism of action could be responsible for the predominantly hypnotic properties of zolpidem and its reduced liability to induce dependence in comparison with benzodiazepines. Yet, several cases of zolpidem abuse and dependence have been published recently. We report seven cases, from which three are detailed, of zolpidem abuse and/or dependence. These patients did not suffer from sedative effects of this drug despite important doses. We even noticed stimulating and euphorising effects in two of these patients, an effect that may explain at least in part the dependence to zolpidem. We will discuss the clinical similarities existing between zolpidem and benzodiazepines' effects. Furthermore we will discuss a molecular genetic hypothesis that may explain the differential effect of a specific benzodiazepine ligand on its receptors.

Manic depressive illness and tyrosine hydroxylase gene: linkage heterogeneity and association.

Several studies have implicated the tyrosine hydroxylase (TH) locus within the 11p15 region in susceptibility to manic depressive illness (MDI). This possibility was further investigated by both parametric (lod score) and nonparametric (affected-pedigree-member and a case-control study) methods of analysis in 11 French MDI families and in a sample of 200 unrelated subjects. Both types of analyses corroborate the implication of this locus, and positive lod scores were obtained in two families, which most likely reflects genetic heterogeneity. Statistical analyses were also performed including available data from published reports. These analyses, which allowed for genetic heterogeneity, substantiated our findings. The combined maximum lod score for all the families studied was 3.68 at theta = 0.00 (number of families: 36) assuming heterogeneity (alpha = 15%, P = 0.01). Taken together these results converge to suggest that the risk factors for MDI lie in the 11p15 region with TH being the most likely candidate gene.

[Epidemiologic and molecular genetic of suicidal behavior]. / Génétique épidémiologique et moléculaire des conduites suicidaires.

The current understanding of suicidal behaviors is that such behaviors are multidetermined and mental state and trait related. Genetic factors appear to be of great importance, as suggested by the findings of family, twin, and adoption studies. Whether these genetic factors are similar to those involved in the susceptibility to psychiatric disorders closely related to suicidal behavior (eg, manic depressive illness, schizophrenia or substance use disorders) is yet unknown. However, a genetic factor of susceptibility to suicide, independent or additive to the genetic transmission of the psychiatric disorders that are related to suicidal behavior, is strongly suggested by the data of the Copenhagen adoption study and a study of Amish families. Recently, new approaches have been proposed to identify the genetic component of such complex traits. Association studies between genetic markers and a disease phenotype has been successfully applied to several complex disease such as essential hypertension. One candidate gene for suicidal behaviors is the tryptophane hydroxylase (TPH) gene which is the first and possibly rate-limiting enzyme of the metabolic pathway for serotonin. Indeed, altered serotoninergic function in both completed suicide and suicide attempt has been one of the most replicated findings in modern biological psychiatry. In our knowledge, only two studies have tested the association between suicide attempt and the TPH gene and their authors found negative results. Despite these negative results, association studies that use candidate gene remain one of the methods of choice for studying the genetic component of suicidal behaviors.

[Value of clozapine in treatment of psychotic disorder in Parkinson disease]. / Intérêt de la clozapine dans le traitement des troubles psychotiques induits de la maladie de Parkinson.

Psychosis secondary to dopaminergic therapy can limit the ability to manage motor symptoms of advanced Parkinson's disease (PD). Scholz and Dichgans (1985) were the first to report the use of clozapine in drug-induced psychosis in PD. The rationale for use of clozapine in parkinsonian patients is supported by his original pharmacological profile with weak extra-pyramidal side effects. A Medline search was performed of literature from 1985 to 1994. The literature search was not limited to the English language. Numerous authors (23 articles) using case reports or open trials among more than 100 patients suggested that clozapine would be useful in treating drug-induced psychosis in PD. We analysed the available information addressing: 1) clinical efficacy, 2) clinical predictors of outcome, 3) delay of action, 4) influence of clozapine on extrapyramidal symptomatology, 5) adverse effects and treatment withdrawal causes, 6) long-term follow-up data. However, the partially negative result of the only double-blind placebo-controlled trials, it may be stated that in some clinical situation of psychosis in PD, the use of clozapine may represent an opportune alternative when other therapeutic strategies have failed.

Tricyclics and malignant syndrome.

A clinical and biological pattern similar to that of neuroleptic malignant syndrome is reported in a depressed patient treated with trimipramine, without any concomitant use of neuroleptics. The antidopaminergic properties of this drug, one of the tricyclic antidepressants, may account for this uncommon side effect.

Suicidal behaviors and the tryptophan hydroxylase gene.

BACKGROUND: To determine whether the tryptophan hydroxylase gene (ie, the gene that codes for the rate-limiting enzyme in the metabolic pathway of serotonin) may be a susceptibility factor for suicidal behavior. METHODS: Genotypic and allelic frequencies at a polymorphic Ava II restriction site were revealed with the use of the complementary DNA tryptophan hydroxylase probe C2-38 in 62 suicide attempters. The psychiatric characteristics of these suicide attempters were determined using the Schedule for Affective Disorders and Schizophrenia-Lifetime version with modification for the study of anxiety disorders, and these characteristics were compared with those in 52 healthy controls. RESULTS: No association between tryptophan hydroxylase and suicidal behavior was detected. CONCLUSION: The tryptophan hydroxylase gene was not a susceptibility factor for suicidal behaviors in the group of suicide attempters in this study.

[Psychosocial stress factors and suicidal acts]. / Facteurs de stress psychosociaux et conduites suicidaires.

Suicidal behaviour is actually understood as being multidetermined and the result of an interaction between state and trait related effects. Several types of risk factors have been extensively studied: psychiatric and personality disorders, genetic variables, biological factors and psychosocial stressors, the latter being the purpose of this review. Social and familial factors, negative life events and medical illness may interact with the factors mentioned above in three main ways to produce suicidal acts: as predisposing factors increasing vulnerability, as precipitating or as contributing factors. A summary of social and clinical studies will be presented and implications for medical care and prevention will be discussed.

[Clinical study of 5 families with bipolar disorder]. / Etude clinique de cinq familles de bipolaires.

Five pedigrees of bipolar patients with at least two bipolar subjects on two generations have been identified in psychiatric departments of Nantes, Montpellier and Challans for linkage studies. In each pedigree, it was found one or more patients suffering from other conditions, like Borderline personality, Anorexia-bulimia, Mental retardation with dysmorphia, and Panic disorders. Mood disorders spectrum and therapeutic implications are discussed.

[Tolerability of tianeptine in 170 patients with depression treated during one year]. / Acceptabilité de la tianeptine chez 170 patients déprimés traités un an.

Tianeptine, a new antidepressant, has a tricyclic molecular structure. Its main biochemical activity consists of an increase in the reuptake of 5 HT both in men and animals, after acute and chronic administration. Tianeptine demonstrated its antidepressive clinical efficacy in several double-blind versus reference drug trials. A multicentre open trial, including depressed patients enabled us to evaluate the safety of tianeptine and to control the maintenance of the therapeutic efficacy in the course of its long-term prescription. Depressed patients included showed a major depressive episode, single (296.22) or recurrent (296.32) without melancholia or psychotic features, or a dysthymic disorder (300.40), according to DSM III criteria. A minimum MADRS score of a least 25, and the informed consent of the patients were required. The dose of tianeptine was 3 tablets per day (12.5 mg/tablet) with the possibility of increasing to 4 or decreasing to 2 tablets per day, depending on the symptomatology. Therapeutic efficacy was evaluated by item 1 and 2 of the Global Clinical Impression (CGI), the Montgomery and Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HARS) and the Hopkins Symptom Check-List (HSCL). Clinical and paraclinical safety were evaluated by CGI item 3, standardized ratings of patients' complaints (CHESS 84), interruption for side effects, evaluation of blood pressure, weight, biological parameters, EKGs. This intermediate evaluation concerns the first 170 depressed patients treated over a one-year period as well as the total group of patients included (n = 447).(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind multicentre comparison of remoxipride, at two dose levels, and haloperidol.

A total of 186 patients who met the DSM-III criteria for schizophrenia were admitted to a double-blind randomized multicentre trial in which the efficacy and safety of remoxipride at two dose levels was compared with those of haloperidol. Over a period of six weeks the patients received remoxipride 100-300 mg/day (n = 60), remoxipride 200-600 mg/day (n = 61), or haloperidol 10-30 mg/day (n = 64). There was no significant difference between the three treated groups with regard to the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores obtained. Remoxipride, at both dosage ranges used, thus had comparable therapeutic efficacy to that of haloperidol. In contrast, extrapyramidal symptoms occurred significantly more frequently in the group treated with haloperidol. Laboratory tests and cardiovascular investigations showed no specific drug effect in any of the treated patients. Remoxipride is thus effective in acute treatment of schizophrenia at both dosage levels and has an advantage over haloperidol in neurological acceptability.

[Use of very high doses of haloperidol in the treatment of acute psychotic episodes. Clinical and pharmacokinetic analysis apropos of 15 cases]. / Utilisation de très fortes posologies d'halopéridol dans le traitement des épisodes psychotiques aigus. Analyse clinique et pharmacocinétique à propos de quinze cas.

High-dosage haloperidol treatment was administered during three weeks in a rapid neuroleptization technique to fifteen patients suffering from acute psychotic episodes. Haloperidol plasma levels were determined by radioimmunoassay. The efficacy of such a therapeutic design seemed fairly good, particularly the rapid improvement during the first week. Yet, tolerance appeared to be low, with a high incidence of adverse effects, some of them unexpected. A very good correlation was observed between haloperidol plasma levels and haloperidol oral doses. By contrast, there was no correlation between plasma levels and clinical improvement. In the same way, the occurrence of adverse effects did not seem to be related to haloperidol plasma levels.