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Lithium is among the most classically recommended add-on therapeutic a strategy for the management of depressive patients showing unsuccessful a response to standard antidepressant medications. a The effectiveness of the add-on strategy with lithium requires achieving a plasma levels above 0.5 mEq/L. a Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate a derivatives or lamotrigine have not demonstrated conclusive therapeutic a effects for the management of depressive patients showing unsuccessful a response to standard antidepressant medications. a Thyroid hormones are considered among the currently recommended add-on a therapeutic strategy for the management of depressive patients showing a unsuccessful response to standard antidepressant medications. a The effectiveness of the add-on strategy with thyroid hormones requires a achieving plasma concentration of TSH close to the lower limits at the a normal range (0.4 mUI/L) or even below it. Second-generation a antipsychotics such as aripiprazole or quetiapine have consistently a demonstrated significant therapeutic effects for the management of a depressive patients showing unsuccessful response to standard a antidepressant medications. a Second-generation antipsychotics however require the careful monitoring a of both cardiovascular and metabolic adverse effects.

Switching antidepressant medication may be helpful in depressed patients a having no benefit from the initial antidepressant treatment. a Before considering switching strategy, the initial antidepressant a treatment should produce no therapeutic effect after at least 4 weeks of a administration at adequate dosage. a Choosing an antidepressant of pharmacologically distinct profile fails a to consistently demonstrate a significant superiority in terms of a effectiveness over the switching to another antidepressant within the a same pharmacological class. a Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most a recommended strategy of antidepressant combinations. a Augmenting SSRI with tricyclic drugs is now a less recommended strategy a of antidepressant combinations given the increased risk for the a occurrence of pharmacokinetic drug-drug interactions and adverse a effects.

IntroductionAntibiomania is characterized by the emergence of a manic episode in reaction to antibiotics. Although relatively uncommon, this kind of side effect is observed in a growing number of cases and mostly occurs in patients who do not have a history of bipolar disorder. Several dozen cases have been reported showing the onset of manic symptoms after taking antibiotics. The antibiotic most frequently involved is clarithromycin.Clinical caseWe report the case of a 61-year-old patient who presented a manic episode after taking an antibiotic combination to treat Helicobacter pylori. Five days after the start of highly active antiretroviral therapy (HAART), behavioral problems appeared (aggressiveness, irritability, talkativeness, insomnia). At the time of hospitalization, she had an acute delusional symptomatology, with a theme of persecution, associated with intuitive, interpretive and imaginative mechanisms. Manic symptoms were obvious: psychomotor excitement, aggressiveness and irritability, flight of ideas, verbal disinhibition and a denial of problems. There was no toxic cause. Brain magnetic resonance imaging (MRI) was normal. Her condition improved very quickly and delusions disappeared in four days. Mrs. H. could critic her delirium and recovered a euthymic state. During hospitalization, treatment divalproate sodium was introduced (250 mg, 3 times a day), was maintained following hospital discharge for 2 years for prevention, and then decreased to the stop. There are currently no further behavioral problems or sleep disorders two years after this episode.DiscussionFacing this clinical case, several questions arise: Which drug therapy is the most suitable for this type of mental disorder? Are there predictors of antibiomania? Is there a risk of recurrence of mood episodes following an antibiomania that occurs spontaneously? What are the pathophysiological mechanisms that could explain this reaction? In all cases identified, stopping the antibiotics was decisive. However, the introduction of a psychotropic and the duration of this treatment remain unclear. First, longitudinal follow-up would assess this variable. Second, it is unclear whether the presence of personal psychiatric history is a predictor of antibiomania. Finally, there are several hypotheses to explain antibiomania: the competitive effect of GABAergic inhibitory receptors, seizure-like phenomena that mimic psychiatric symptoms, and disruption of the intestinal microbiota by antibiotics leading to a modification of the functioning of the central nervous system. The explanatory model of antibiomania is not yet known and requires further research., L’antibiomania se définit par l’apparition d’un épisode maniaque en réaction à la prise d’antibiotiques. Ce phénomène, bien qu’assez rare, n’est pas négligeable étant donné le nombre croissant de cas observé. Il se manifeste en général chez des sujets n’ayant pas d’antécédent de trouble bipolaire. Nous décrivons le cas d’une patiente de 61 ans qui a présenté un épisode maniaque suite à la prise d’une trithérapie antibiotique reçue pour l’éradication d’Helicobacter pylori dans le cadre d’un ulcère gastroduodénal. À l’arrêt du traitement antibiotique, les symptômes maniaques ont régressé en quelques jours. Plusieurs questions se posent notamment sur l’attitude thérapeutique à adopter et les causes expliquant l’antibiomania. Celles-ci sont encore floues. Nous abordons par ailleurs plusieurs hypothèses étiologiques : l’effet compétitif inhibiteur au niveau des récepteurs gabaergiques, l’effet épileptogène mimant un tableau psychiatrique, et la perturbation du microbiote intestinal par les antibiotiques, modifiant de façon indirecte le fonctionnement du système nerveux central.

International audience; IntroductionAntibiomania is characterized by the emergence of a manic episode in reaction to antibiotics. Although relatively uncommon, this kind of side effect is observed in a growing number of cases and mostly occurs in patients who do not have a history of bipolar disorder. Several dozen cases have been reported showing the onset of manic symptoms after taking antibiotics. The antibiotic most frequently involved is clarithromycin.Clinical caseWe report the case of a 61-year-old patient who presented a manic episode after taking an antibiotic combination to treat Helicobacter pylori. Five days after the start of highly active antiretroviral therapy (HAART), behavioral problems appeared (aggressiveness, irritability, talkativeness, insomnia). At the time of hospitalization, she had an acute delusional symptomatology, with a theme of persecution, associated with intuitive, interpretive and imaginative mechanisms. Manic symptoms were obvious: psychomotor excitement, aggressiveness and irritability, flight of ideas, verbal disinhibition and a denial of problems. There was no toxic cause. Brain magnetic resonance imaging (MRI) was normal. Her condition improved very quickly and delusions disappeared in four days. Mrs. H. could critic her delirium and recovered a euthymic state. During hospitalization, treatment divalproate sodium was introduced (250 mg, 3 times a day), was maintained following hospital discharge for 2 years for prevention, and then decreased to the stop. There are currently no further behavioral problems or sleep disorders two years after this episode.DiscussionFacing this clinical case, several questions arise: Which drug therapy is the most suitable for this type of mental disorder? Are there predictors of antibiomania? Is there a risk of recurrence of mood episodes following an antibiomania that occurs spontaneously? What are the pathophysiological mechanisms that could explain this reaction? In all cases identified, stopping the antibiotics was decisive. However, the introduction of a psychotropic and the duration of this treatment remain unclear. First, longitudinal follow-up would assess this variable. Second, it is unclear whether the presence of personal psychiatric history is a predictor of antibiomania. Finally, there are several hypotheses to explain antibiomania: the competitive effect of GABAergic inhibitory receptors, seizure-like phenomena that mimic psychiatric symptoms, and disruption of the intestinal microbiota by antibiotics leading to a modification of the functioning of the central nervous system. The explanatory model of antibiomania is not yet known and requires further research.; L’antibiomania se définit par l’apparition d’un épisode maniaque en réaction à la prise d’antibiotiques. Ce phénomène, bien qu’assez rare, n’est pas négligeable étant donné le nombre croissant de cas observé. Il se manifeste en général chez des sujets n’ayant pas d’antécédent de trouble bipolaire. Nous décrivons le cas d’une patiente de 61 ans qui a présenté un épisode maniaque suite à la prise d’une trithérapie antibiotique reçue pour l’éradication d’Helicobacter pylori dans le cadre d’un ulcère gastroduodénal. À l’arrêt du traitement antibiotique, les symptômes maniaques ont régressé en quelques jours. Plusieurs questions se posent notamment sur l’attitude thérapeutique à adopter et les causes expliquant l’antibiomania. Celles-ci sont encore floues. Nous abordons par ailleurs plusieurs hypothèses étiologiques : l’effet compétitif inhibiteur au niveau des récepteurs gabaergiques, l’effet épileptogène mimant un tableau psychiatrique, et la perturbation du microbiote intestinal par les antibiotiques, modifiant de façon indirecte le fonctionnement du système nerveux central.

International audience; INTRODUCTION: Bipolar disorder (BD) is a life course illness; and there is increasing awareness of the many personal, social and economic consequences of the illness in older adults. However, it is important to emphasize that BD usually begins in late adolescence or early adulthood and 75 % cases have a first episode in this age period. This early onset and the associated level of disability mean that BD is the 4th leading cause of global disease burden in adolescents and young adults. Internationally, mental health services are increasingly striving to diagnose and treat BD as early as possible to try to prevent poor outcomes. In addition, researchers are using methods employed previously in psychosis studies as these may help us to recognise the earliest manifestations of BD. If it is possible to identify sub-threshold and 'ultra high risk' syndromes for BD, this might lead to new interventions that could target the prevention of first episodes of mania. One approach to understanding these risk syndromes is to examine prospective community cohort studies and BD offspring studies. METHODS: This paper reviews prospective cohort studies that identify robust risk factors in early illness onset, which was defined as age at onset of BD between 15-25 years. RESULTS: We found that although > 50 % of individuals who developed BD had developed a putative BD prodrome prior to 14 years of age, this usually began with non-specific symptoms that overlap with similar presentations for those who later develop psychosis or severe depression. However, there are some features that seem to better identify groups with a BD "at-risk" syndrome. This syndrome is frequently composed of several factors such as mood lability, depressive episodes, prior anxiety, sleep and/or conduct disorders, attention and concentration impairment, altered energy patterns, and a family history of mania and/or depression. The course of these early predictors suggests the precursor syndromes are composed of mini-clusters of symptoms many of which are episodic and change over time. During the early phases of BD, most of the affective disturbances reported were depressive in polarity and started during adolescence, there were few manic or mixed or psychotic episodes with an onset before puberty. The pathogenesis of BD demonstrates a gradual progression from non-specific to more specific symptoms and then to frank BD features. CONCLUSION: Prospective community and offspring BD cohort studies are approaches that together can help us understand the evolution of BD and allow us to define the developmental pathways. Further, identifying subjects with BD "at-risk" syndrome using a clinical staging model may allow benign interventions to be used as first-line treatment - such as neuroprotective agents like essential fatty acids; second line treatments, with a less benign risk to benefit ratio should be reserved for severe or resistant cases.

International audience; SOURCE MONITORING FRAMEWORK: Source monitoring refers to the ability to remember the origin of information. Three source monitoring processes can be distinguished: external source monitoring, internal or self-monitoring and reality monitoring (i.e. discrimination between internal and external sources of information). Source monitoring decisions are based on memory characteristics recorded such as perceptions, contextual information or emotional reactions and heuristic or more controlled judgement processes. BRAIN STRUCTURES: Several studies suggested that specific structures in the prefrontal and the mediotemporal lobes are the main areas implicated in source monitoring. ASSESSMENT: A typical source monitoring paradigm includes an items generation stage and a second stage of recognition of items (old versus new) and identification of their sources: external (usually the examiner) or internal (the subject). Several indices can be calculated based on the raw data such as the number of false alarms, attribution biases or discrimination indexes. To date, there is no standardized source monitoring task and differences in the type of items used (words, pictures), in the cognitive or emotional effort involved or in the delay between the two test stages, contribute to the heterogeneity of results. FACTORS INFLUENCING SOURCE MONITORING: Factors such as age (either very young or very old) and emotions influence source monitoring performances. Influence of gender was not properly explored, whereas the role of IQ and selective attention is still debated. SOURCE MONITORING DEFICITS IN NEUROLOGICAL DISORDERS: Source monitoring deficits are observed mainly in disorders affecting frontotemporal areas, such as frontal trauma, Alzheimer's disease or frontotemporal dementia. SOURCE MONITORING AND SCHIZOPHRENIA: Source monitoring errors (e.g. external misattribution of self-generated information) are observed in schizophrenia and seem to correlate with positive symptomatology, in particular auditory hallucinations, thought intrusion and alien control symptoms. These results are of particular interest in clinical research because source monitoring is one of the rare cognitive tests showing a correlation with the positive dimension. Source monitoring deficits have been proposed as a potential explanation for the positive symptoms and some, but not all studies lent support to this hypothesis. Heterogeneity of studied samples, in particular different criteria to define hallucinating subjects (e.g. currently versus anytime during their lives), could explain the discordant results. SOURCE MONITORING IN PSYCHIATRIC DISORDERS WITHIN THE SCHIZOPHRENIC SPECTRUM: Source monitoring impairments were observed in pharmacological models of psychosis, in first degree relatives of schizophrenic patients, and also in the general population associated with schizotypal dimensions. These results support a relationship between source monitoring deficits and some of the symptomatic dimensions of the schizophrenic spectrum but still await replication. SOURCE MONITORING AND OTHER PSYCHIATRIC DISORDERS: Some studies found source monitoring deficits in other psychiatric conditions such as mania or obsessive-compulsive disorder. Thus, those studies suggest that source monitoring deficits may be not specific to schizophrenia. CONCLUSION: Source monitoring competencies are critical for good (i.e. adapted) everyday functioning. Source monitoring deficits have been suggested as a potential explanation for some (or all) positive psychotic symptoms. However, to date, methodological inconsistencies (especially with regard to test design and choice of subjects' samples) have precluded firm, definite conclusions.

International audience; No abstract available

International audience; BACKGROUND: After stopping a 3 to 6 months course of oral anticoagulation for a first episode of idiopathic venous thromboembolism (VTE), the risk of recurrent VTE is high (10% per year). In this setting, international guidelines recommend at least 6 months treatment. However, this recommendation is not satisfactory for the following reasons: (1) no randomized trial has compared 6 months to extended duration (2 years) anticoagulation; and (2), even though the frequency of recurrent VTE is similar after pulmonary embolism (PE) and deep vein thrombosis (DVT), the fatality rate of recurrent VTE after PE is higher than that after DVT. METHODS: A French multicentre double blind randomized trial. The main objective is to demonstrate, after a first episode of symptomatic idiopathic PE treated for 6 months using a vitamin K antagonist, that extended anticoagulation for 18 months (INR between 2 and 3) is associated with an increased benefit / risk ratio (recurrent VTE and severe anticoagulant-related bleeding) compared to placebo. The double blind evaluation is ensured using by active warfarin and placebo, and blinded INR. The protocol was approved by the ethics board of the Brest Hospital on the 7th of March 2006. For an alpha risk of 5% and a beta risk of 20%, the estimated sample size is 374 patients. EXPECTED RESULTS: This study has the potential to: (1) demonstrate that the benefit / risk ratio of extended anticoagulation for 18 months is higher than that observed with placebo in patients with a first episode of idiopathic PE initially treated for 6 months, during and after the treatment period; and (2) to validate or invalidate the contribution of isotope lung scans, lower limb Doppler ultrasound and D-Dimer at 6 months of treatment as predictors of recurrent VTE (medico-economic analysis included).

International audience; OBJECTIVE: This report describes the psychometric evaluation of the French translation of the Signs and Symptoms of Psychotic Illness (SSPI) scale. The SSPI scale was designed to assess the five main clusters of symptoms of people suffering from psychotic disorders (psychomotor poverty, reality distortion, disorganisation, depression, and psychomotor excitation) across diagnostic entities. This new tool has been built by Liddle because, in the existing scales assessing psychotic symptoms, individual items cover symptoms that belong to different pathophysiological processes. The SSPI scale comprises 20 items. Its interview is semi-standardised and typically lasts around 25 min. The English version of this scale has shown good psychometric properties (inter-rater reliability, factor structure). METHOD: We used the SSPI ratings of 81 patients with psychotic symptoms to assess its factor structure and concurrent validity with the Clinical Global Impressions (CGI) scale. Twenty-eight videotaped ratings were used to calculate the intra-class correlation coefficient (ICC) as a measure of inter-rater reliability. RESULTS AND DISCUSSION: The sample was composed of 46 schizophrenic subjects, 14 with schizoaffective disorder, three with major depressive episode with psychotic features, nine with manic episode with psychotic features and nine with other psychotic disorders. A principal component analysis was conducted to determine the factor structure. Using the Cattell test, we retained a five-factor solution. This solution explained 56.9% of the variance. After varimax rotation, 18 items were attributed to a unique factor. The five factors were: a psychomotor poverty factor, a reality distortion factor, a disorganised factor, an anxious/depressive factor and a psychomotor excitation factor. This structure is close to the original one. The inter-rater reliability of the French version of the SSPI was satisfactory for 18 items, with a mean ICC of 0.64 for the individual items, and an ICC of 0.76 for the global scale. Only two items had an unsatisfactory ICC. This scale showed a good correlation with the CGI scale, with a correlation coefficient between CGI score and SSPI global score of 0.64. Among the factor scores, reality distortion, disorganisation and depression factor scores exhibited a significant correlation with the CGI score. CONCLUSIONS: The French version of the SSPI scale has good psychometric properties, similar to the English version. Furthermore, its factor structure is similar to the English one. This scale is a robust instrument to rate psychotic symptoms and dimensions across diagnosis entities.

Since the serendipitous discovery of typical antipsychotics in the treatment of schizophrenia, several molecules have been developed for their tolerance and a specific action. However, before any prescription of these molecules, in the spirit of the disorder, the concept of resistance to the treatment was evoked. Indeed, there is an inter-individual variation of response to antipsychotics in schizophrenic subjects that was described by specific scales of evaluation. It appears that clinical factors seem to contribute to the non response of treatment and they are not appreciated so well. Psychotics follow specific pathways and it is know that physiological and biochemical effects depend on factors. Thus, smoking habits, alcohol and diet have been described as factors influencing variability in drug response. While age, gender and genetic factors seem to contribute to the quality of therapeutic response. Evidence from family, twin and adoption studies clearly demonstrate the involvement of genetic factors in schizophrenia. Both linkage and association studies support this hypothesis. Although the results of such studies remain inconsistent regarding the heterogeneity of the disease. Refinement of the phenotype using the pharmacogenetic approach could thus be useful in the genetic studies of schizophrenia. Pharmacogenetic research claim to assess a possible interaction between the therapeutic targets of antispychotics and their specific mutations in candidate genes. High affinity of atypical antipsychotics for 5-HT2A receptors may explain their specific efficacy/tolerability profile compared to conventional antipsychotics. A number of reports have associated a silent 5-HT2A polymorphism (T102) with response to clozapine or risperidone. This polymorphism is in complete linkage disequilibrium with a -1438A/G polymorphism, located within the promoter region of the gene, with conflicting results. Phenotypical heterogeneity of schizophrenia might explain such discrepancies. For example, negative symptoms are known to reflect severity of illness and to restrain therapeutic response. On this basis, we re-assessed the possible influence of the −1438A/G polymorphism of the 5-HT2A receptor gene on the clinical efficacy of atypical antipsychotics with focus on several relevant dimensions. The A allele and the AA genotype of the −1438A/G polymorphism of the gene coding for the 5-HT2A receptor were not associated with therapeutic response to atypical antipsychotics in our sample. Furthermore, the AA genotype appeared to be associated with the SANS score, raising the possibility that negative symptoms in schizophrenia constitute a confounding factor between the 5-HT2A gene and atypical antipsychotic response. Traditionally, dopaminergic and serotoninergic sytems have been used as targets for antipsychotic therapy. Although, most available antipsychotics have a multitarget profile without any clear mechanism of action. Recently, atypical antispychotics have been found to display a wide range of affinities for several neurotransmitters. Neurobiological research suggest a significant role of the endocannabinoid system in schizophrenia vulnerability and also in the quality of response to antipsychotics. Epidemiology studies show that patients consume twice more of cannabis than the general population. An increase of the density of receptors is observed in the dorsolateral prefrontal cortex of schizophrenic post mortem samples. The CNR1 gene, that encodes the CB1 receptor, is located on chromosome 6q14-15, which has been considered as a susceptibility locus for schizophrenia. Recent progress in pharmacogenetics, evaluating the individual risk for antipsychotic refractoriness, has focused notably on the dopaminergic and serotoninergic systems. However, so far, these studies led to discrepant data. This led us to assess the possible influence of the 1359G/A polymorphism as a haplotype tagging SNP of the CNR1 gene, in comparison with three other SNPs covering 14kb across this gene, on the risk of schizophrenia and/or therapeutic response to atypical antipsychotics. We found no difference in 1359G/A polymorphism between patients and control subjects, and no relationships were noted between this polymorphism and any clinical parameter considered as potential intermediate factor. However, the G allele frequency was significantly higher among non-responsive vs responsive patients, with a dose effect of the G allele. In contrast, no association was found for three other genetic polymorphisms of the CNR1 gene. Pharmacogenetics may in future lead to individualized pharmacotherapy based on the specific genetic, environmental and demographic characteristics of each patient. Pharmacogenetics could thus increase the patient comfort in terms of both higher initial response rates and reduced propensity to developing debilitating side-effects., Depuis la découverte, fruit du hasard des neuroleptiques pour traiter la schizophrénie, de nombreuses molécules ont été développées pour une meilleure tolérance et une meilleure efficacité. Toutefois, bien avant la prescription de ces molécules, à l'essence même de la pathologie, le concept de résistance a été évoqué. La variabilité interindividuelle de réponse aux antipsychotiques des sujets schizophrènes a pu être ainsi conceptualisée grâce à des échelles spécifiques d'évaluation. Il apparait que ces sujets non répondeurs se caractérisent par une symptomatologie clinique plus bruyante qui n'est pas toujours évaluée de manière spécifique par ce type d'échelles. Les psychotropes empruntent des voies bien définies et il est reconnu que les effets physiologiques et biochimiques de ces substances sont soumis à certaines influences. Ainsi, le type d'alimentation, l'alcool et le tabac sont autant de facteurs extrinsèques influant la réponse aux traitements tandis que l'âge, le sexe, le poids ou d'autres facteurs physiopathologiques (incluant les facteurs héréditaires) sont d'importants facteurs intrinsèques. L'hypothèse d'un sous bassement génétique de la schizophrénie est étayé par plusieurs travaux comme les études épidémiologiques, de liaison génétique et des gènes candidats. Toutefois, l'hétérogénéité phénotypique de la maladie amène à des résultats variables. De fait, le cloisonnement phénotypique à la non réponse aux antipsychotiques chez les patients schizophrènes, pourrait être contributif à ce type d'approche. La pharmacogénétique se base sur les connaissances pharmacologiques des antipsychotiques et des gènes candidats des récepteurs cibles de ces molécules. Se basant sur l'hypothèse sérotoninergique de la schizophrénie et le tropisme préférentiel des antipsychotiques atypiques pour le récepteur sérotoninergique 5-HT2A, les premières études dans ce domaine ont testé la qualité de la réponse à la clozapine avec les polymorphismes T102C -1438A/G de la région promotrice et du gène du récepteur 5-HT2A. On peut toutefois noter l'inconsistance des résultats. L'hétérogénéité phénotypique de la maladie pourrait, au travers de symptômes cliniques, souligner ces différences. Par exemple, les symptômes négatifs dont la constance au cours de la maladie et l'association avec une moins bonne réponse thérapeutique sont reconnus. Notre hypothèse était que la disparité des résultats des études pharmacogénétiques testant le gène du récepteur 5-HT2A était liée à l'interférence des symptômes négatifs eux-mêmes sous influence génétique. Nous avons donc choisi de tester le polymorphisme -1438A/G de la région promotrice du gène codant pour le récepteur 5-HT2A et la réponse aux antipsychotiques, évaluant de manière parallèle les variables cliniques pouvant aggraver la réponse aux traitements. Dans ce premier travail, nous avons constaté que les sujets mauvais répondeurs se définissent surtout par la gravité des symptômes négatifs. Nous ne retrouvons pas d'association positive entre le polymorphisme génétique -1438A/G et la réponse aux antipsychotiques atypiques. Toutefois, l'allèle A et le génotype AA semblent être significativement associés à l'intensité des symptômes négatifs intervenant ainsi comme potentiel facteur confusionnant dans les études pharmacogénétiques testant le récepteur 5-HT2A. Les théories dopaminergiques et sérotoninergiques dans la schizophrénie ont été enrichies d'autres hypothèses pharmacologiques comme l'implication des systèmes adrénergiques, histaminiques, muscariniques ou cannabinoides. Plusieurs arguments permettaient d'envisager le gène du récepteur CB1 comme potentiellement impliqué dans la réponse médicamenteuse chez les patients schizophrènes. La plupart des études épidémiologiques montrent que les patients schizophrènes consomment jusqu'à deux fois plus de cannabis que dans la population générale. Les études post mortem réalisées chez les patients schizophrènes montrent une augmentation de la densité de ces récepteurs au niveau du cortex préfrontal dorsolatéral et cela de manière indépendante à la consommation récente de cannabis. La localisation cérébrale des récepteurs CB1, leur rôle interactif avec d'autres neurotransmetteurs en particulier la dopamine ou le glutamate ont permis d'envisager l'hypothèse endocannabinoide de la schizophrénie. Le gène du récepteur CB1 est localisé sur la région chromosomique 6q14-15, une région potentiellement impliquée dans la schizophrénie. Dans un second travail, nous avons analysé le polymorphisme 1359G/A du récepteur CB1 (étant donné sa caractéristique de tag-SNP) dans la réponse aux antipsychotiques. Parallèlement, nous avons choisi de tester trois autres polymorphismes couvrant environ 14kb du gène du CB1. Nous trouvons une association significative entre l'allèle G et la mauvaise réponse aux antipsychotiques mais pas d'association avec la maladie. Les travaux de recherche en pharmacogénétique semblent pertinents dans la prédiction de la qualité de la réponse aux traitements chez les patients schizophrènes. Dans la mesure où les mécanismes d'actions des antipsychotiques sont connus, il semble aisé de tester les gènes des récepteurs cibles dans la prédiction de la réponse médicamenteuse. Ce type d'approche pourrait être contributive comme outil complémentaire au psychiatre afin d'améliorer le confort des patients à travers une meilleure compliance.

BACKGROUND: The schizotypal personality disorder is a recent psychiatric nosological concept developed by Spitzer at the end of the 1970s, based on the analysis of the characteristics of relatives of schizophrenic subjects included in the adoption studies carried out in the same decade by Kety, Wender and Rosenthal. HISTORICAL ASPECTS: However, this entity is based on older observations, at the beginning of the past century, showing common behavioural characteristics in relatives of schizophrenics. Its status within our current nosography remains dubious, sometimes classified among personality disorders, sometimes in the schizophrenia spectrum disorders. It is interesting to present the origins of this concept that stem from two complementary approaches: a family approach and a clinical approach of sporadic cases and then to redefine the framework within which the diagnostic approach was based and its continuity, up until our current classifications, the DSM and CIM. CURRENT STATUS: The historical origins cannot summarize the disorder and it appears important to redefine the multidimensional characteristics of the schizotypal personality disorder, generally a three-factor model. Indeed, dimensional models of psychosis are becoming established as conceptually and clinically useful. Recent studies on the dimensionality of psychosis show an evolution of the schizotypal concept, initially defined as being part of the schizophrenia spectrum and which now appears to be more broadly linked to a concept of unitary psychosis, including the bipolar disorder. CONCLUSION: Dimensions of psychosis seem to be associated with different familial aggregation and risk of psychosis, suggesting that they are underlined by different physiopathological processes. Hence, the dimensional approach can help to disentangle the genetic heterogeneity of the disease.