David Gourion

Contexte : La preualence de l'episode depressif majeur (EDM) tend a augmenter avec l'âge et la reconnaissance de ce trouble chez les patients tres âges, est rendue difficile par leur presentation clinique particuliere dominee par l'anxiete et les plaintes somatiques. Il n'existe pas d'auto-questionnaire specifique pour l'aide au depistage de l'EDM chez les patients tres âges de plus de 75 ans qui soit valide en langue francaise. Objectif : Construire et valider un questionnaire pour le depistage de l'EDM apres 75 ans. Methode : Un questionnaire initial de 38 items a ete propose a l'aide des criteres diagnostiques d'EDM et de dysthymie du Mini-International Neuropsychiatrie Interieur (MINI) (selon le DSM-IV) et de l'avis d'experts cliniciens geriatres et psychiatres. Une deuxieme etape a permis de mettre en place une etude de validation chez 190 patients souffrant de depression et 179 sujets controles selectionnes dans une population de...

Un jeune adulte sur quatre est en situation de mal-etre psychique. Il est plus que temps d'agir ! Anxiete, stress, insomnies, fatigue, perte de motivation : il est souvent bien difficile chez les 15-30 ans de faire la part des choses entre difficultes psychologiques passageres et vrais symptomes psychiatriques. Or le reperage des premiers signes de fragilite est fondamental. David Gourion, a partir de son experience de psychiatre, presente dans ce livre de nouvelles pistes concretes et utiles pour aider les jeunes adultes et leurs parents a construire un avenir souriant.

UNLABELLED Minor Physical Anomalies represent valuable indices of disturbance in early neurodevelopment. They are frequently observed in individuals with various brain disorders, including mental retardation, autism, epilepsy, hyperactivity, foetal alcohol syndrome and schizophrenia. The high prevalence of Minor Physical Anomalies in schizophrenia provides considerable support for a neurodevelopmental model in this disorder. However, studies in large sample using standardised scale are lacking. Such studies are needed in order to confirm their actual frequency and study the clinical correlates or morphological anomalies. OBJECTIVE The aim of this study was to revise and validate a French version of a scale designed for the evaluation of Minor Physical Anomalies in adult psychiatric patients and notably in patients with schizophrenia. METHODOLOGY The scale was revised from the Waldrop scale. The choice of items was done on the basis of frequency, reliability in the adult, reliability...

RESUME Mal-etre, incertitudes face aux conditions de vie a l’âge adulte, nostalgie de l’enfance fondent la crise de l’adolescence. Attitudes de revolte, conflits avec l’environnement, echecs d’orientation scolaire ou sociale, mise en danger de soi ne sont pas synonymes de menaces d’evolution psychopathologique. Il appartient au medecin de savoir discerner les indices preoccupants tels que dysmorphobie, angoisse existentielle ou sentiment de vide, rupture de la trajectoire scolaire ou sociale. Trop souvent l’identification d’un trouble psychiatrique n’est faite que tardivement, apres plusieurs annees d’evolution. Le suicide est la deuxieme cause de mortalite a l’adolescence. Tout geste suicidaire impose une evaluation au cours de quelques jours d’hospitalisation en milieu psychiatrique. Les antidepresseurs peuvent etre necessaires et utiles chez l’adolescent deprime : c’est bien la depression et non les antidepresseurs qui pose une grave question de sante publique.Les troubles des conduites alimentaires sont surtout frequents chez la jeune fille. Il importe d’identifier les comorbidites psychiatriques : schizophrenies, depression, trouble obsessionnel compulsif, et de prendre au serieux le risque vital.Les usages et abus de toxiques sont frequents a l’adolescence : pres de la moitie des jeunes adolescents en France ont consomme une fois au moins du cannabis. La encore il importe d’identifier les comorbidites psychiatriques.La phobie est un trouble anxieux trop meconnu. Elle peut s’organiser en trouble chronique generateur de souffrance et de handicap. Enfin deux grandes pathologies psychiatriques debutent a l’adolescence : schizophrenies et troubles bipolaires. Il faut evoquer ces diagnostics aussi precocement que possible pour mettre en oeuvre des strategies therapeutiques adaptees. Il convient de denoncer l’usage trop frequent du diagnostic d’etat limite, ecran a un diagnostic plus precis et entrave a des therapeutiques dont l’efficacite sera amoindrie par le retard a les mettre en oeuvre.

Resume L’enjeu de la formation pour les psychiatres liberaux est complexe et crucial. En effet, comment concilier, d’une part, une pratique clinique extremement prenante et chronophage et ses corollaires (charges administratives, certificats, appels et exigences croissantes des patients, situations d’urgence complexes…) et, d’autre part, la necessite d’une mise a jour reguliere des connaissances dans une discipline en mutation permanente (avancees des neurosciences, complexification des strategies psychopharmacologiques, diversification des psychotherapies…). Le piege est souvent de parer au plus presse, a savoir la clinique, au detriment de la formation.

Les signes neurologiques mineurs frequemment retrouves chez les patients schizophrenes temoignent d'une vulnerabilite developpementale globale puisque cette derniere deborde les seules fonctions cognitives. Certains patients presentent en effet des troubles moderes de la coordination motrice, de l'integration sensorielle et motrice ou encore de la lateralisation. Ces signes existent avant meme la mise sous traitements neuroleptiques. Ils constituent un marqueur prodromique puisque des donnees suggerent qu'ils constituent un facteur de risque pour la schizophrenie, et cela des l'enfance. Une meilleure caracterisation clinique, neuroradiologique et genetique de ces signes neurologiques pourrait conduire vers de nouvelles perspectives dans notre connaissance de la physiopathologie des troubles schizophreniques.

The uncertainties of looming adulthood, nostalgia for childhood, and a general malaise explain the crisis of adolescence. Rebellion, conflict, occasional failure at school or in society, and at-risk behaviors are not always signs of future psychiatric illness. In contrast, the physician must be in a position to identify tell-tale signs such as dysmorphophobia, existential anxiety, a feeling of emptiness, and school or social breakdown. Most psychiatric disorders that begin in adolescence are only diagnosed several years after onset. Yet early diagnosis is of utmost importance, as treatment becomes less effective and the long-term prognosis worsens with time. Suicide is the second cause of death during adolescence. All signs of suicidal behavior require hospitalization and evaluation in a psychiatric unit. Antidepressants may be necessary in adolescence. The recent controversy concerning a possible increase in the suicidal risk during antidepressant treatment should not mask the fact...

The selective serotonin reuptake inhibitors (SSRIs) have emerged as a major therapeutic advance in psychiatry. They have emphasized the pathophysiological role of serotonin (5-HT) in affective disorders. Indeed, SSRIs were developed for inhibition of the neuronal uptake for serotonin (5-HT), a property shared with the TCAs (tricyclic anti-depressants), but without affecting the other various central neuroreceptors (ie, histamine, acetylcholine and adrenergic receptors) that are responsible for many of the safety and tolerability problems with TCAs. In this way, fluoxetine and other SSRIs represent a major advance over tricyclics, because of their lower toxicity. While the position of fluoxetine relative to other selective serotoninergic antidepressants requires further investigation, fluoxetine has a more favorable tolerability profile for a similar efficacy in comparison to tricyclic antidepressants. The pharmacokinetic and pharmacodynamic properties of fluoxetine are well describe...

Minor Physical Anomalies represent valuable indices of disturbance in early neurodevelopment. They are frequently observed in individuals with various brain disorders, including mental retardation, autism, epilepsy, hyperactivity, foetal alcohol syndrome and schizophrenia. The high prevalence of Minor Physical Anomalies in schizophrenia provides considerable support for a neurodevelopmental model in this disorder. However, studies in large sample using standardised scale are lacking. Such studies are needed in order to confirm their actual frequency and study the clinical correlates or morphological anomalies. The aim of this study was to revise and validate a French version of a scale designed for the evaluation of Minor Physical Anomalies in adult psychiatric patients and notably in patients with schizophrenia. The scale was revised from the Waldrop scale. The choice of items was done on the basis of frequency, reliability in the adult, reliability of rating. Some new items, relat...

We examined the test-retest reliability of the Temperament and Character Inventory (TCI) in a clinical sample of 29 inpatients with opiate dependence disorder (DSM-IV). The previously validated French translation of the TCI was administered at baseline and again four weeks later. Intraclass correlation coefficients (ICCs) were used to estimate stability of the TCI over time for the 15 patients who completed the study. For all ICCs, the TCI showed satisfactory to excellent stability across all factors (ICC= 0.66-0.82). Stability was lower for the two temperamental traits of 'persistence' (ICC=0.51) and 'reward dependence' (ICC=0.63), possibly reflecting both clinical instability and measurement errors. These results highlighted the overall stability of the TCI in patients with opiate dependence and provided evidence for the usefulness of this questionnaire, which was originally designed to explore genetic and environmental factors underlying normal and abnormal personality dimensions. Further studies are required to confirm these results on larger clinical samples.

One of the main features of schizophrenia is its age at onset in early adulthood. Dopaminergic dysregulation is the most documented neurobiological factor that may be involved in triggering schizophrenia. Recent findings on neurodevelopmental processes show that the brain-derived neurotrophic factor plays a critical role in the development of mesolimbic dopaminergic-related systems and regulates the expression of dopamine D3 receptors. In this study, we examine whether an interaction between dopamine D3 receptors and brain-derived neurotrophic factor gene variants influences age at onset in patients with schizophrenia. Our findings show that this gene-gene interaction was significantly associated with an earlier emergence of psychosis by 3 years.

Resume Malgre de nombreuses avancees dans le traitement pharmacologique de la depression, environ 30 % des patients deprimes resistent a au moins deux antidepresseurs. L’evolution peut alors conduire vers la chronicite, avec un impact considerable en termes de qualite de vie et de cout pour la societe. Dans cette revue critique de la litterature, nous resumons les donnees d’etudes controlees et de meta-analyses afin de mettre en relation la recherche actuelle avec la pratique clinique. Les strategies de potentialisation de l’antidepresseur incluent l’ajout d’un autre antidepresseur synergique, des antipsychotiques atypiques, du lithium, du pindolol, des psychostimulants, du pramipexole et des estrogenes. Dans l’ensemble, les strategies de potentialisation les plus efficaces permettent d’obtenir des taux de remission entre 25 et 50 % avec des NNT compris entre 3 et 8. Parmi ces options, les potentialisations par les APA, la T3 et le pramipexole semblent offrir le meilleur rapport benefice–risque. Toutes ces prescriptions se font hors AMM.

La depression bipolaire demeure largement sous-diagnostiquee, tandis que les strategies de traitement sont encore insuffisamment codifiees. A ce jour, peu de molecules ont fait la preuve de leur efficacite curative. Seules l’associationolanzapine-fluoxetine et la monotherapie quetiapine ont montre une superiorite vis-a-vis du placebo. Ce n’est le cas ni des sels de lithium, du valproate ou de la lamotrigine, ni de l’aripiprazole. L’efficacite de la quetiapine, nouvel antipsychotique atypique aux proprietes thymoregulatrices, est liee a son profil psychopharmacologique original. La quetiapine combine antagonisme D2 et 5HT2, agonisme 5HT1A et effet noradrenergique puissant via son metabolite actif, la norquetiapine. Ses effets indesirables les plus frequents associent sedation, hypotension, secheresse de la bouche et prise moderee de poids. Comme le suggerent les grandes recommandations internationales, la quetiapine tient desormais une place de choix dans l’arsenal therapeutique dedie a la prise en charge des depressions bipolaires.

Neurological soft signs (NSS) and minor physical anomalies (MPA) are frequent in patients with schizophrenia and their biological relatives. We examined whether the NSS and MPA are related to the genetic loading in schizophrenia. Patients with schizophrenia (DSM-IV) (n=61), nonpsychotic parents of these patients (n=76) and healthy comparison subjects (n=44) took part in the study. Parents were further classified as "presumed carriers" of the genetic loading (n=26) if they had a second relative with schizophrenia in their ascendants and/or collaterals (first or second degree) or as "presumed noncarriers" (n=50). NSS and MPA were compared in these groups. A multivariate analysis indicated that total NSS and MPA scores, adjusted for age and gender, were significantly related to group status. Univariate tests showed higher scores in motor coordination and integration subscores (p=0.005 and 0.008, respectively) in presumed carriers than in presumed noncarriers. In addition, a discriminant function analysis based on total NSS and MPA scores correctly classified 71% of nonpsychotic parents in presumed carriers or presumed noncarriers. Neurological impairments and slight morphological anomalies seem to be associated with the genetic risk for schizophrenia, even when the disease itself is absent. Their presence might be a valuable composite intermediate phenotype for genetic studies.

Schizophrenia is characterized by thought disorders, hallucinations and delusions. Genetic studies have shown a high linkage at chromosome 6q16-21. Among the genes located in this region is the glutamate receptor ionotropic kainate 2 gene (GRIK2 or GLUR6), a functional candidate for susceptibility to schizophrenia. In this study, transmission of GRIK2 was evaluated in 356 schizophrenic patients from three different clinical centers. Whereas paternal transmission shows equilibrium, we observed maternal transmission disequilibrium of GRIK2 in the largest population (p=0.03), which was still significant when all populations were added (p=0.05). These results are similar to the maternal GRIK2 transmission disequilibrium previously reported for autism, and support the presence of a susceptibility gene for schizophrenia at 6q16.

Serotonin (HT) and noradrenaline (NA) reuptake inhibitors (SNRIs) are commonly used as first line treatment of major depressive disorders (MDD). As compared to tricyclic antidepressants, they have proved similar efficacy and better tolerability. Milnacipran (MLN) (Ixel) and venlafaxine (VLF) (Effexor) are two SNRIs pharmacologically differing by their NA/HT ratio of potency: 1:1 and 1:30, respectively. To investigate the efficacy and safety/tolerability of MLN and VLF administered at flexible doses (100, 150 or 200 mg/day) for 24 weeks (including 4 weeks of up-titration) in the outpatient treatment of adults with moderate-to-severe MDD. Multicentre, randomised, double blind, 2-parallel-arm, 24-week exploratory trial conducted in France by 50 psychiatrists. DIAGNOSIS AND MAIN INCLUSION CRITERIA: Male or female outpatients, aged 18 to 70, meeting the DSM-IV-TR and related MINI criteria for recurrent, unipolar, moderate-to-severe MDD, with neither psychotic features nor severe suicidal risk. A Montgomery-Asberg depression rating scale (MADRS) score> or =23 was required at inclusion. TREATMENT SCHEDULE: Patients were randomised to receive either MLN or VLF (1:1 ratio) for 24 weeks in double-blind conditions. Regardless of the treatment received, the following dosing schedule was applied: during the initial 4-week up-titration phase, the dosage was progressively increased from 25 mg/day (qd administration) to 150 mg/day (bid administration). At week 4, the dosage was either maintained at 150 mg/day, or adapted to 100 or 200 mg/day, based on the investigator's clinical judgement. At any time during the 20 following treatment weeks, the dose could be lowered for safety concerns until a minimal threshold of 100 mg/day. From Week 24, the dosage was decreased by 50mg/day every five days. After randomisation, eight assessment visits were organised at 2, 4, 6, 8, 12, 18, 24 weeks, and at study end (after the 5-15 days of down-titration and 10 days free of treatment). Efficacy evaluation ratings included the MADRS and global disease severity (CGI-S) total scores. Rates of MADRS response (reduction of initial score> or =50%) and remission (score< or =10) were calculated at Week 8 and Week 24 in the full analysis set as well as in the subgroups of patients with depressive disorder of severe DSM-IV intensity and with a MINI evaluation of suicidal risk (rated as required 'moderate' at the worst). Standard distribution statistics (including mean and standard deviation [S.D.]) of scores and their changes from baseline, were calculated using the observed-case (OC) approach at all assessment times for the MADRS score, and the last-observation-carried-forward (LOCF) at 8 and 24 weeks for both MADRS and CGI-S scores. MADRS response and remission rates at 8 and 24 weeks were calculated using the LOCF approach by normal approximation of the binomial distribution. Bilateral exploratory statistical tests at 5% significance level were performed for results at 8 and 24 weeks of: (i) MADRS score changes from baseline, based on the score progress at each visit (mixed model for repeated measurements [MMRM]), and (ii) global MADRS response and remission rates (Chi(2)). RESULTS AND PATIENTS: A total of 195 patients were randomly assigned MLN (n=97) or VLF (n=98) and 134 (68.7%: 61.9%/MLN and 75.5%/VLF) completed the trial. At the end of the up-titration, patients received 100 mg/day (11.4%/MLN, 10%/VLF), 150 mg/day (30.4%/MLN, 43.8%/VLF), or 200 mg/day (58.2%/MLN, 46.3%/VLF). Totals of 177 patients (90/MLN and 87/VLF) and 181 patients (90/MLN and 91/VLF) were analysed for efficacy and safety, respectively. Treatment groups were similar for baseline characteristics except a higher proportion of MLN patients with a severe depressive episode (63.3% versus 54%). RESULTS AND EFFICACY: MADRS score (mean [S.D.] initial score: 31 [4.5]) progressively decreased all along the treatment course and similarly in both groups (Week 8-OC : -18.8 [7.7]/MLN and -18.6 [7.3]/VLF, p(MMRM)=0.95 ; Week 24-OC : -23.1 [7.8]/MLN and -22.4 [7.3]/VLF, p(MMRM)=0.37 ). At week 8-LOCF, MADRS response rates were similar in both groups (64.4%/MLN, 65.5%/VLF, p(chi2)=0.88) as well as remission rates (42.2%/MLN, 42.5%/VLF p(chi2)=0.97). At week 24 they remained non clinically and statistically different between groups (response rates: 70%/MLN, 77%/VLF, p(chi2)=0.29; remission rates: 52.2%/MLN, 62.1%/VLF, p(chi2)=0.19). In both "severe depressive episode" and "MINI mild or moderate suicidal risk" subgroups (n=104 and 75, respectively), response and remission rates were non clinically different at both time points, however in the "MINI mild-to-moderate suicidal risk" subgroup, MLN tended to be more rapidly active (remission rate at week 8-LOCF: 44.7%/MLN, 35.1%/VLF). The changes in CGI-S were also indicative of a significant improvement of the global illness severity with both treatments. RESULTS AND SAFETY/TOLERABILITY: The…

The switch is generally admitted as one of the available options in the event of non-response to an antidepressant treatment, despite uncertainties about its implementation in current practice: what time window before switching? Is it necessary to proceed with a direct or with a gradual switch? Is it necessary to change for a different pharmacotherapeutic class? How to minimize interaction risks? If a treatment fails because of poor compliance due to intolerance, it is possible to remain within the same therapeutic class and select another treatment with a more favourable safety profile for the patient. In the remaining non-response cases, changing therapeutic class is the more logical course and may be slightly more efficacious than the switch within the same class. A review of the literature shows that it is recommended to wait 4 to 8 weeks before changing treatment if the response is insufficient. However, an early switch is possible in case of non-response at 2-4 weeks. Direct switch is possible and well tolerated in most instances, except for situations implicating a monoamine oxidase inhibitor (MAOI) or a tricyclic antidepressant. Direct switch is easy and, therefore, compliance issues associated with the complexity of treatment tapering can be avoided. From the pharmacologic standpoint, the lack of effect on the cytochrome P450 isoenzymes, the absence of active metabolites, and the poor binding to plasmatic proteins are all important elements to be identified in order to minimize the risk of interaction. Current research on physiopathology of depression and mechanisms of action of drugs both support expectations for new perspectives for patients' care. The switch increases the chances for a treatment to be successful with response rates of 20 to 70% in the open-labelled clinical studies. It also has the advantage of minimizing adverse effects compared to polytherapy. A great number of depressed patients require more than one treatment protocol to obtain or maintain a response. Switching is part of the therapeutic pattern of depression and is recommended by the French authorities. The available data allow the specification of switch modalities as function of the evolution of the initial treatment.

Many hypotheses have been made to explain the high rate of benzodiazepine consumption in France, including a general cultural and/or familial tendency to use certain types of psychotropic drugs. This study explored the association between lifetime medication use by parents and their children. Two hundred and twenty-one young patients (158 boys and 63 girls) consulting at a child and adolescent psychiatry department, six to 16 years of age (mean = 9.7 years), were screened for lifetime use of psychotropic drugs using a structured interview. Parents were asked about their own consumption, as well as their children’s. Lifetime consumption rates (at least once) were 22.2% in boys and 20.6% in girls, and 19.6% in children less than 11 years old. Higher rates were found in patients with emotional disorders (anxiety disorders and depression). In parents, 45.1% of mothers and 24.1% of fathers reported using medications at least once. A significant association was found between child and par...