Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment and self-reported side effects in the euthymic phase of bipolar disorders: Results from the FACE-BD cohort.

Bipolar disorders (BD) are characterized by cognitive impairment during the euthymic phase, to which treatments can contribute. The anticholinergic properties of medications, i.e., the ability of a treatment to inhibit cholinergic receptors, are associated with cognitive impairment in elderly patients and people with schizophrenia but this association has not been well characterized in individuals with remitted BD. Moreover, the validity of only one anticholinergic burden scale designed to assess the anticholinergic load of medications has been tested in BD. In a literature review, we identified 31 existing scales. We first measured the associations between 27 out of the 31 scales and objective cognitive impairment in bivariable regressions. We then adjusted the bivariable models with covariates: the scales significantly associated with cognitive impairment in bivariable and multiple logistic regressions were defined as having good concurrent validity to assess cognitive impairment. In a sample of 2,031 individuals with euthymic BD evaluated with a neuropsychological battery, two scales had good concurrent validity to assess cognitive impairment, whereas chlorpromazine equivalents, lorazepam equivalents, the number of antipsychotics, or the number of treatments had not. Finally, similar analyses with subjective anticholinergic side-effects as outcome variables reported 14 scales with good concurrent validity to assess self-reported peripheral anticholinergic side-effects and 13 to assess self-reported central anticholinergic side-effects. Thus, we identified valid scales to monitor the anticholinergic burden in BD, which may be useful in estimating iatrogenic cognitive impairment in studies investigating cognition in BD.

Acute and Post-Traumatic Stress Disorders: A biased nervous system.

Acute stress disorder and post-traumatic stress disorder are generally triggered by an exceptionally intense threat. The consequences of this traumatogenic situation are explored here in chronological order, from exposure to the threat to development of symptoms. Such a situation may disrupt the equilibrium between two fundamental brain circuits, referred to as the "defensive" and "cognitive". The defensive circuit triggers the stress response as well as the formation of implicit memory. The cognitive circuit triggers the voluntary response and the formation of explicit autobiographical memory. During a traumatogenic situation, the defensive circuit could be over-activated while cognitive circuit is under-activated. In the most severe cases, overactivation of the defensive circuit may cause its brutal deactivation, resulting in dissociation. Here, we address the underlying neurobiological mechanisms at every scale: from neurons to behaviors, providing a detailed explanatory model of trauma.

Evaluation de la douleur et de l'anxiété lors de soins dentaires chez les patients hospitalisés en psychiatrie.

OBJECTIF: La santé bucco-dentaire des patients en psychiatrie est problématique, puisque le recours au chirurgien-dentiste demeure inférieur de 25 % à la population générale. En partant de ce postulat, nous avons souhaité comprendre en quoi l'anxiété et la douleur du patient peuvent impacter la prise en charge bucco-dentaire et le bon déroulement des soins. MÉTHODE: Cette étude a été menée sur 100 patients hospitalisés en psychiatrie. Grâce à différentes échelles, nous avons évalué leur niveau d'anxiété et de douleur, mais aussi leur coopération aux soins. RÉSULTATS: L'anxiété ne constitue pas un frein à la prise en charge, et diminue significativement après les soins. Le comportement durant les soins bucco-dentaires des patients hospitalisés en psychiatrie semble similaire à celui de la population générale. CONCLUSION: Notre étude permet de mieux appréhender les soins dentaires en psychiatrie et devrait contribuer à placer les soins dentaires au centre de la prise en charge somatique en psychiatrie.

[Association between the violence in the community and the aggressive behaviors of psychotics during their hospitalizations]. / Relation entre la violence intra-hospitalière des patients avec psychoses et la violence dans la communauté.

BACKGROUND: Violence is a common issue in psychiatry and has multiple determiners. The aim of this study is to assess the psychotic inpatients' violence in association with the violence of the neighborhood from which the patients are drawn and to estimate the impact of this environmental factor with regard to other factors. METHOD: A prospective multicenter study was led in nine French cities. Eligible patients were psychotic involuntary patients hospitalized in the cities' psychiatric wards. During their treatments, any kind of aggressive behavior by the patients has been reported by the Overt Aggression Scale (OAS). RESULTS: From June 2010 to May 2011, 95 patients have been included. Seventy-nine per cent of the patients were violent during their hospitalizations. In a bivariate analysis, inpatient violence was significantly associated with different factors: male gender, patient violence history, substance abuse, manic or mixed disorder, the symptoms severity measured by the BPRS, the insight degree and the city crime rate. In a multivariate analysis, the only significant factors associated with the patients' violence were substance abuse, the symptoms severity and the crime rates from the different patients' cities. CONCLUSION: These results suggest that violence within the psychotic patients' neighborhood could represent a risk of violence during their treatments.

Brain connectivity and auditory hallucinations: In search of novel noninvasive brain stimulation therapeutic approaches for schizophrenia.

Auditory verbal hallucinations (AVH) are among the most characteristic symptoms of schizophrenia and have been linked to likely disturbances of structural and functional connectivity within frontal, temporal, parietal and subcortical networks involved in language and auditory functions. Resting-state functional magnetic resonance imaging (fMRI) has shown that alterations in the functional connectivity activity of the default-mode network (DMN) may also subtend hallucinations. Noninvasive neurostimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) have the ability to modulate activity of targeted cortical sites and their associated networks, showing a high potential for modulating altered connectivity subtending schizophrenia. Notwithstanding, the clinical benefit of these approaches remains weak and variable. Further studies in the field should foster a better understanding concerning the status of networks subtending AVH and the neural impact of rTMS in relation with symptom improvement. Additionally, the identification and characterization of clinical biomarkers able to predict response to treatment would be a critical asset allowing better care for patients with schizophrenia.

Alteration of pain recognition in schizophrenia.

BACKGROUND: Schizophrenia patients display impaired recognition of their own emotions and those of others and deficits in several domains of empathy. The first-person experience of pain and observing others in pain normally trigger strong emotional mechanisms. We therefore hypothesized that schizophrenia patients would display impaired recognition and categorization of both their own pain and the pain of others. METHODS: We studied 29 patients (18 men/11 women; 36 ± 13 years old) with paranoid schizophrenia-spectrum disorder and 27 healthy volunteers (20 men/7 women; 31 ± 9 years old) matched for age, gender, IQ and socio-cultural level. We assessed symptom severity and theory of mind. The participants' ability to detect and categorize pain in others was assessed with the sensitivity to expressions of pain (STEP) test, which is based on facial expressions, and another dynamic test involving a series of video sequences showing various pain-inducing events. The ability of patients to evaluate their own pain was assessed with the situational pain questionnaire (SPQ), which includes a series of questions assessing how one would expect to feel in different imaginary situations. Empathic tendencies were assessed with the interpersonal reactivity index. RESULTS: Patients and controls differed significantly in STEP, pain video and SPQ scores. By contrast with control subjects, the patients' pain judgements were not correlated with their affective or cognitive empathic capacities. CONCLUSIONS: Schizophrenic patients have a deficit of the identification and categorization of pain both in themselves and in others.

[Humour and the theory of mind in schizophrenia: a review of the literature]. / Humour et théorie de l'esprit dans la schizophrénie, revue de la littérature.

Humour is a universal phenomenon, a daily fact holding positive aspects valued in society. The sense of humour is subjective, inherent in each and everyone and difficult to assess. We could qualify it as an indefinable sense set by an absence of norms. This intangible notion occupies a primordial social role of communication, confidence, shared by all with both therapeutic and physical benefit. Scientists started researching this theme in schizophrenic patients from 1950. Studies show a net deficit of humour capabilities between healthy subjects and patients. The hypothesis of a deficit of the theory of mind in the evaluation of humour in schizophrenics is currently the object of several experiments. Nowadays, cognitive functions are also taken into account in humour perception studies. However the little or few studies relevant to this subject are a definite obstacle to the understanding of this complex phenomenon.

[The placebo effect: general information and specificities in psychiatry (depression and schizophrenia)]. / L'effet placebo : généralités et spécificités en psychiatrie (dépression et schizophrénie).

INTRODUCTION: Placebos, consequences of their use, the placebo effect and the associated negative effects, the nocebo effect, have been widely studied. However, the lack of any consensus definition makes the interpretation and analysis of such findings difficult. LITERATURE FINDINGS: In this article, we will review existing definitions and factors affecting the placebo effect in medicine. We will then consider the possible mechanisms of action of the placebo effect, with a view to improving understanding of this issue. Finally, we will analyse data relating to placebos used in psychiatry and, more specifically, for schizophrenic patients. In an extensive review of the literature, we identified the various factors playing a role in the appearance of placebo effects in general medicine. As well as purely factual elements, such as the disorder, the sex of the subject and the treatment given, the placebo effect is strongly correlated with the quality of the relationship between the doctor and patient and with the capacity of the patient to communicate and establish a link. The attitude of the doctor, the temperament of the subject and the expectations and beliefs of each also contribute to the appearance and extent of a placebo effect. We then investigated placebo effects in psychiatry, particularly in depressed patients (the most widely studied condition) where studies have shown particular efficacy. We also addressed the use of placebos in schizophrenia: the placebo effect in patients with this disorder is essentially used as a tool for assessing new molecules to be released onto the market but the phenomenon itself has been little studied, if at all. Thus, it is of particular interest to consider in detail the use of placebos in schizophrenia, to try to gain a deeper understanding of the factors involved. This will allow potential specific effects associated with placebo use in this disorder to be established, improving the integration of placebos into therapy and to optimize the efficacy of treatment prescribed, taking into account mental state; indeed, the placebo effect is present in all treatments, whether involving a placebo or an active compound.

[Long-term impact of the diagnostic announcement on the insight of patients suffering from schizophrenic disorders]. / Impact à long terme de l'annonce diagnostique sur l'insight de patients atteints de troubles schizophréniques.

INTRODUCTION: The importance of insight in patients with schizophrenia is linked to the notion that few subjects are conscious of their pathology and that some treatments fail due to a lack of consciousness of the necessity of medication. Since then, studies have been frequently undertaken into the insight of schizophrenic patients. It is believed that a good degree of insight could influence the quality of acceptance by the patient of the disease. This would facilitate closer medicinal supervision, resulting in fewer relapses and thus a decrease in the number of hospitalizations and subsequent improved quality of life for the patients. In 2002, a protocol of diagnostic announcement was set up for schizophrenic patients in the Ville-Evrard Hospital. Two years later, we observed a high level of compliance in these patients (70 %). AIM OF THE STUDY: The aim of our new study is therefore to assess insight in stabilized schizophrenic patients having benefited from the protocol of diagnostic announcement and to compare their degree of insight with a control population. METHOD: Two scales of insight were used: the hetero-questionnaire Scale to Assess Unawareness of Mental Disorder (SUMD, Schizophr Bull 17 (1991) 113-32), and the self-questionnaire: Self Appraisal of Ilness Questionnaire (SAIQ, Schizophr Res 45 (2000) 203-11). The clinical symptom of psychosis was assessed by the Positive and Negative Syndrome Scale (PANSS). The Man and Whitney Test was used for the quantitative data and the exact Fisher test for qualitative data. RESULTS: A total of 31 patients were included, 15 in the group having received the diagnostic announcement - population with protocol (P) and 16 in the control group without protocol (SP). The socio-demographic data analysis of the population P (having received the diagnostic announcement) showed a younger population with a shorter evolution of the disease compared to the population "SP". The P group is in demand as regards information on their disorders. In addition, in patients having lived with this disease for many years, these episodes have taken on a taboo status compared to patients in the early stage of the disease. One can consider that the psychiatrists proposed this psycho-informative protocol to younger patients. The results obtained with the SUMD scale were improved in the population "P" as regards development of insight (significantly with the factor 5). Attribution (factor 5) is the factor which the patients had the greatest difficulty estimating. Attribution is the result of external training, rather than awareness which solicits greater introspection. Therefore, psycho-education support played the role of "apprenticeship". Degree of insight was globally of good quality in this questionnaire (compared with the self-questionnaire). Results of the self-questionnaire: SAIQ shows that the degree of insight is quite low in both populations. Few authentic and reflected answers were possible in either of the two groups. However, the presence of a correlation between the overall two scores confirms that we did assess the same phenomenon. The PANSS clinical evaluation shows that the population "P" has symptoms of lesser intensity overall and significantly fewer positive symptoms than the population "SP". The limits of our study are linked to the small number of patients included, despite a homogeneous sample. CONCLUSION: In conclusion, the protocol of diagnostic announcement and psycho-education have helped stabilize schizophrenic patients in order to improve their insight, without increasing the intensity of this disease in the short- or long-term. Work on insight should allow a new understanding of the patient's relation with the disease along with the medical team and his close relations.

[Pain and schizophrenia: myth and reality]. / Douleur et schizophrénie: mythe et réalité.

INTRODUCTION: The International Association for the Study of Pain (IAPS), in 1986, defined pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage". Thus, the few studies on this phenomenon conducted on schizophrenic patients did not result in a firm consensus; certain studies showed that such patients seemed to have a higher threshold against pain (hypoalgesia) than healthy subjects, whilst other studies showed that the threshold is the same, but the absence of expressing the pain would be due to the pathology itself (non-expression of the pain, denial). Insensitivity to pain would be the consequence of a complex reaction between a biological sensorial abnormality and the psychopathology of schizophrenia itself (including the affective processes). Hence, various hypotheses referring to biological, psychological and sociological mechanisms have been proposed. BIOLOGICAL THEORIES: Various other hypotheses based on biological factors have been suggested. One of the interesting biologically-based hypotheses postulates that the insensitivity is due to a dysregulation of N-methyl-d-aspartate (NMDA). The biological factors are still not fully explored and would only explain in part the phenomenon of the apparent insensitivity to pain of individuals with schizophrenia. PSYCHOLOGICAL THEORIES: The thresholds of pain and a higher level of tolerance could be explained by an indifference to external stimuli and by inappropriate mental functions for these tests. The deficit is situated, therefore, both in the sensory discrimination of the stimulus (biological function) but also in the interpretation (cognitive and emotional functions). These different hypotheses (biological and psychological) might explain the insensitivity to pain of schizophrenic patients. PAIN AND SCHIZOPHRENIA: THE REALITY: Schizophrenic patients have a sensitivity to pain which is identical to that of healthy subjects. The apparent analgesia would be the result of a denial "attitude", a different manner of expressing pain in relation with the non-verbal communication difficulties, and not an alteration in the brain functions nor a biological anomaly. Diverse methodological biases arise from the studies of pain in patients with schizophrenia.

Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia.

Non-invasive unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex induces analgesic effects in focal chronic pain syndromes, probably by modifying central pain modulatory systems. Neuroimaging studies have shown bilateral activation of a large number of structures, including some of those involved in pain processing, suggesting that such stimulation may induce generalized analgesic effects. The goal of this study was to assess the effects of unilateral rTMS of the motor cortex on chronic widespread pain in patients with fibromyalgia. Thirty patients with fibromyalgia syndrome (age: 52.6 +/- 7.9) were randomly assigned, in a double-blind fashion, to two groups, one receiving active rTMS (n = 15) and the other sham stimulation (n = 15), applied to the left primary motor cortex in 10 daily sessions. The primary outcome measure was self-reported average pain intensity over the last 24 h, measured at baseline, daily during the stimulation period and then 15, 30 and 60 days after the first stimulation. Other outcome measures included: sensory and affective pain scores for the McGill pain Questionnaire, quality of life (assessed with the pain interference items of the Brief Pain Inventory and the Fibromyalgia Impact Questionnaire), mood and anxiety (assessed with the Hamilton Depression Rating Scale, the Beck Depression Inventory and the Hospital Anxiety and Depression Scale). We also assessed the effects of rTMS on the pressure pain threshold at tender points ipsi- and contralateral to stimulation. Follow-up data were obtained for all the patients on days 15 and 30 and for 26 patients (13 in each treatment group) on day 60. Active rTMS significantly reduced pain and improved several aspects of quality of life (including fatigue, morning tiredness, general activity, walking and sleep) for up to 2 weeks after treatment had ended. The analgesic effects were observed from the fifth stimulation onwards and were not related to changes in mood or anxiety. The effects of rTMS were more long-lasting for affective than for sensory pain, suggesting differential effects on brain structures involved in pain perception. Only few minor and transient side effects were reported during the stimulation period. Our data indicate that unilateral rTMS of the motor cortex induces a long-lasting decrease in chronic widespread pain and may therefore constitute an effective alternative analgesic treatment for fibromyalgia.

[Pharmacogenetics and treatment response in schizophrenia]. / Approche pharmacogénétique de la réponse aux antipsychotiques chez les schizophrènes. Revue de la littérature.

UNLABELLED: The pharmacogenetic strategy uses the genetic association approach with the aim of identifying genes that influence clinical response to drug treatment. Association studies have focused mainly on neuroleptics (in particular clozapine) and variants in candidate genes of dopamine and serotonin systems in schizophrenic patients. Concerning the serotonin 5-HT(2A) receptor gene, the frequency of allele tyrosine (versus histidine) at 452 was greater among nonresponders, and homozygosity for the cytosine allele at 102 was more frequent among nonresponders. In the serotonin 5-HT(2C) receptor gene, a cysteine to serine substitution at 23 was considered as a predictor of good response to clozapine. Concerning the dopamine D2 receptor gene, the patients with one or two A1 alleles showed greater improvement than those with no A1 allele (Taq1A genotype). In addition, compared with patients who exhibited a Del allele at 141, patients with no Del allele showed better clinical response. Regarding the dopamine D3 receptor gene, the homozygous genotype serine/serine at 9 was found to be more frequent among the nonresponders. Finally, there was a possible relationship between the 48 bp variant number tandem repeat polymorphism in dopamine D4 receptor gene and response to neuroleptics. DISCUSSION: However, some results conflict with other data in the literature. The frequent difficulties in replication of pharmacogenetic findings can be explained by, among others: (i) the lack of a consistent definition of drug response; (ii) the use of different scales to evaluate response to treatment and the use of several cut-offs for the same scale; (iii) the sample heterogeneity and the small sample size; and (iv) the multigenic interactions. In order for research to progress, methodological consistency must be achieved, not only to form the basis of comparison among studies and to confirm or invalidate previous results, but also to allow for meta-analysis between the various studies. Nevertheless Kane et al. [Arch Gen Psychiatry 45 (1988) 789-796] have defined precise criteria of clinical response, but they are restrictive and quite difficult to set up in practice. Pharmacogenetic research has the following advantages: (i) it is based on the individual patient's genotype, invariable data in normal conditions, and can therefore be measured at any time during treatment; (ii) it uses reliable molecular biological techniques; and (iii) it is in constant progress because of the increasing amount of genomic information available. CONCLUSION: In future, a combination of several polymorphisms showing a strong association with a specific neuroleptic response could constitute a clinical test to predict the individual response to such treatment, and therefore participate in the prescription process. A research team has already proposed a combination of six polymorphisms implicating 5-HT(2A) receptor, 5-HT(2C) receptor, 5-HTTLPR, and H2 receptor genes [Lancet 355 (2000) 1615-1616], but this result has to be replicated. Until now, pharmacogenetics has focused on the global clinical response, but in the years to come, it could focus on the genes implied in the effects of treatments on specific symptoms and on physiological mechanisms that would explain how gene polymorphism can influence therapeutic response. This review aims to summarise recent advances and to present future clinical applications for pharmacogenetics.

Transcranial magnetic stimulation in the treatment of schizophrenic symptoms: a double blind sham controlled study.

BACKGROUND: Schizophrenia is a disabling disease with a significant proportion of patients experiencing persistent symptoms. Repetitive transcranial magnetic stimulation (rTMS) is a promising new therapeutic tool that could benefit to schizophrenic patients. In this study we sought to assess the efficacy of active rTMS compared to sham stimulation in the treatment of patients with schizophrenia. METHOD: Eighteen schizophrenic patients according to DSM-IV criteria were randomly allocated to receive active or sham rTMS for 10 days over the left temporoparietal cortex (80% of the motor threshold, 1Hz, five trains of 1 min). Psychopathological dimensions were measured with the positive and negative syndrome scale and clinical global impression at baseline and after 10 session of rTMS. RESULTS: All patients were improved at the end of the trial but no significant group differences were found. Patients receiving sham stimulation showed the same pattern of improvement compared to active condition on all the subscales of the positive and negative syndrome scale and clinical global impression scores (p>0.05). CONCLUSION: In our study, active rTMS failed to show superiority over sham stimulation in the treatment of schizophrenic symptoms. Although previous results have shown that rTMS reduces auditory hallucination, its efficacy on other positive schizophrenic symptoms is not yet established. Nevertheless, the results of our study, even though negative, provide further insights in the pathophysiology of schizophrenia.

[Schizophrenia diagnostic announcement in a French psychiatric unit]. / Annonce du diagnostic de schizophrénie au sein d'un service de psychiatrie de secteur.

Announcement of schizophrenia diagnostic to the patients is a topical issue in France. The evolution in clinical practices, a better efficiency in therapeutic procedures and the fundamental right of the patient to obtain information have initialised the discussion of its interest. Spontaneous claim for information from the patient is rarely observed although awareness troubles might be reported at the instauration of the mental disorder or during its evolution. Methodological studies concerning the diagnostic announcement are limited. Except the Bayle studies recently published, only a few publications are available in France about the knowledge of their pathology and their need to be clearly informed. French scientific literature deals generally about medico-legal aspects of this information and consisted of survey about diagnostic announcement. International literature is more abundant and presents positive and negative aspects of the announcement. An information procedure of schizophrenia announcement to the patient has been developed in our hospitalisation unit of psychiatry. This procedure has taken place on the basis of the literature data, our specificity and our clinical experiences. For some Anglo-American psychiatrists who have proceeded to semi-structured interview in order to announce the diagnostic, information to the patients might improve the clinical relationship. Thus, compliance to the treatment is significantly increased. The ability of the patient to recognise the symptoms of the disease and to accept their consequences and the treatments is associated to a better social prognosis, daily activities and response to the treatment. The announcement impact justifies the prescription of neuroleptics, treatment that is notoriously perceived as prejudicial by the patients themselves or more commonly in the basic population. To obtain compliance to the treatment, a satisfactory acceptance of the mental disorder is required. Compliance is based on satisfactory information in order to gain the cooperation of the patient and its relative (10). Atkinson has classified four main types of arguments, the ethical principle to be informed, talk to explain and give sense to the symptoms, reduce the feeling of guilt perceived by the patient and his relative and enhance the collaboration between the patient and the nursing staff. According to Ferreri and Bayle studies French psychiatrists reluctance to announce schizophrenia diagnostic are the following: lack of request or of interrogations asked by the patient about their disease, diagnostic and prognosis uncertainty and irreversibility of the disease, complexity of the pathology and its origin which hinder an accessible explanation, cognitive disorders frequently observed with schizophrenic patients which may be associated with difficulties of understanding information, destabilization of the patient-nursing staff relationship and social stigmatisation risks. Other arguments like reluctance to give a "label" to the disease, too abstract diagnostic, a negative social vision and the possibility of discouragement for the relative are classically retrieved in French literature. In fact, divulgation of the term schizophrenia involves a panel of negative representations and is hindered by the confusion in the social imagination of such a term related with lost of control, quintessence of madness, dangerous behaviour possibilities, evil and incurability. Some psychiatrists do not transmit information arguing that significant obstruction of the future may be consecutive to the information. They prefer to use vague terms more socially acceptable like "nervous breakdown or depression, atypical or emotional disorder, dissociative troubles...". Information to the patient about his mental disorder is more frequent in psychiatry for affective, anxious and additive troubles than for schizophrenia. Our procedure of diagnostic announcement has been elaborated after preliminary discussion with the medical and nursing staff. Diagnostic of schizophrenia announcement has been presented by weighing the pros and cons according to the intemational literature. It clearly appeared that benefits for the patients prevail on the drawbacks. Nevertheless, inclusion and clinical supervision have to be carefully precised in particular to verify the ability to receive information. Short term objectives: deliver progressively information to the patient about his disease by means of an active and educational process with hope and optimism using a accessible language (explanation of each terms used with the intention of being well understood); quantify the impact of diagnostic announcement on the schizophrenic patient using clinical rating scales during a period of one month (clinical interview at day 1, day 7 and day 28). Mid term objectives: improve the global supervision and autonomy of schizophrenic by means of a therapeutic project helping the patient to become an active partner in the monitoring of his mental disorder; enhance a psycho-educational program after the procedure of announcement in order to optimise the observance of his treatment, increase his quality of life and answer to the requests of his relative; 45 patients (age 29.3 +/- 8.8 years old) have been included to be informed on their diagnostic since the elaboration of this procedure during a time period of 24 months. Time interval between the beginning of their pathology and the delivering of this information was 4.7 years. Most of them (56%) presented a paranoid type of schizophrenia. In most of the cases, the patients did not know their diagnostic or declared suffering from a diagnostic, which was erroneous; 80% of the 45 patients have complied with the procedure until its end. On more than 24 of following after the instauration of the diagnostic announcement procedure, these patients ha ve presented satisfactory observance to the medical supervision (medical consultation and drug intake); 60% of the patients were regularly present to their medical appointment. The number of patients included (45 patients) appears small compared to the time interval of the study (24 months) but was significant according to the great changes in our clinical approach. Thus, this procedure was not systematically applied, in particular the patients who did not want to be informed on their disease. Is it clinically relevant or not to announce diagnostic of schizophrenia to the patient? This issue remains questioned according to the few studies published at the present time, any consensus has been clearly presented on formal indications or contra-indications. If on an ethical side, this information appears logical, the medical and nursing staff should require special care. Special care must be taken before delivering information to the patients; each situation must be evaluated in order not to comply with an ideology of total and inadequate information, which could have serious consequences. Nevertheless, it appeared clearly that information must be given to stabilized patients with satisfactory insight. Moreover, psychotherapeutic projects become easier because patients awareness and understanding towards pathological symptoms are greatly improved. Partnership between patient and medical staff is the key of this dynamic and psycho-educative procedure, which opens new horizons in our therapeutic prospect.

[Transcranial magnetic stimulation in cognition and neuropsychology]. / Stimulation magnétique transcrânienne et fonctions cognitives.

Classical neuropsychology relies on patients with irreversible brain lesions and cognitive impairments give informations about normal brain function. Transcranial Magnetic Stimulation (TMS) is a non-invasive method which involves placing an electromagnetic coil on the scalp. A pulse generates a magnetic field and this one passes, unattenuated by the skin and scalp, into the cortex inducing a current which results in neural activity. The technique shows a good temporal resolution and, moreover, because it represents an interference technique, can be said to have excellent functional resolution. For this reason, TMS appears to be a new tool for research in neuropsychology, producing transitory 'virtual lesion'effects which could help to understand how, when and where cognitive tasks are performed. The purpose of this article is to review recent research using TMS in cognition and neuropsychology, in a non exhaustive way. In safety studies, single TMS over motor cortex can produce simple movements. Several groups have applied TMS to the study of visual processing and found an impaired detection of visual stimuli. In a same way, TMS can disrupt speech when it was delivered in the language dominant hemisphere. Studies on the memory effects of TMS have been conflicting and the results seem to depend on the choice of paradigm and parameters. Other study depicted improvements in executive functioning after TMS on the left middle frontal gyrus or a diminution in reaction time during an analogic reasoning task. Moreover, some facial emotions seem to be less recognizable after TMS. Although TMS seem to be a new tool for neuro-psychological investigations in healthy subjects, few studies reported cognitive effects of rTMS treatment in psychiatry. In a therapeutic view, many of these trials have supported a significant effect of TMS, but in some studies the effect is small and short lived. Several groups have reported on the use of rTMS as a treatment in resistant major depression and the impact on cognition functioning. Most of results tend to find no adverse cognitive effects after several weeks of daily rTMS in depressed patients, compared to Electroconvulsivo-therapy (ECT). The effects of transcranial magnetic stimulation (TMS) on hallucination severity and neurocognition were studied in a recent study. A statistically significant improvement was observed on a hallucination scale and on one cognitive measure. TMS is a promising tool for cognitive neuroscience and can provide complementary information to the one obtained using neuropsychological tests, and the one obtained using functional imaging techniques, which have superior spatial but inferior temporal resolution.

Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype.

To determine if neuregulin 1 (NRG1) is associated with schizophrenia in Asian populations, we investigated a Han Chinese population using both a family trio design and a case-control design. A total of 25 microsatellite markers and single nucleotide polymorphisms (SNPs) were genotyped spanning the 1.1 Mb NRG1 gene including markers of a seven-marker haplotype at the 5' end of the gene found to be in excess in Icelandic and Scottish schizophrenia patients. The alleles of the individual markers forming the seven marker at-risk haplotype are not likely to be causative as they are not in excess in patients in the Chinese population studied here. However using unrelated patients, we find a novel haplotype (HAP(China 1)), immediately upstream of the Icelandic haplotype, in excess in patients (11.9% in patients vs 4.2% in controls; P=0.0000065, risk ratio (rr) 3.1), which was not significant when parental controls were used. Another haplotype (HAP(China 2)) overlapping the Icelandic risk haplotype was found in excess in the Chinese (8.5% of patients vs 4.0% of unrelated controls; P=0.003, rr 2.2) and was also significant using parental controls only (P=0.0047, rr 2.1). A four-marker haplotype at the 3' end of the NRG1 gene, HAP(China 3), was found at a frequency of 23.8% in patients and 13.7% in nontransmitted parental haplotypes (P=0.000042, rr=2.0) but was not significant in the case-control comparison. We conclude that different haplotypes within the boundaries of the NRG1 gene may be associated with schizophrenia in the Han Chinese.

[Catatonia: resurgence of a concept. A review of the international literature]. / La catatonie: résurgence d'un concept. Une revue de la littérature internationale.

Catatonia was first described in 1874 by Kahlbaum as being a cyclic disease mixing motor features and mood variations. Because most cases ended in dementia, Kraepelin recognized catatonia as a form of dementia praecox and Bleuler included it within his wide group of schizophrenias. This view influenced the psychiatric practice for more than 70 years. But catatonia was recently reconsidered and this because of the definition of more precise diagnosis criteria, the discovery of a striking association with mood disorders, and the emphasis on effective therapeutics. Peralta et al empirically developed a performant diagnostic instrument with the 11 most discriminant signs among catatonic features. Diagnostic threshold is three or more signs with sensitivity of 100% and specificity of 99%. These signs are: immobility/stupor (extreme passivity, marked hypokinesia); mutism (includes inaudible whisper); negativism (resistance to instructions, contrary comportment to whose asked); oppositionism, other called gegenhalten (resistance to passive movement which increases with the force exerted); posturing (patient adopts spontaneously odd postures); catalepsy (patient retains limb positions passively imposed during examination; waxy flexibility); automatic obedience (exaggerated co-operation to instructed movements); echo phenomena (movements, mimic and speech of the examiner are copied with modification and amplifications); rigidity (increased muscular tone); verbigeration (continuous and directionless repetition of single words or phrases); withdrawal/refusal to eat or drink (turning away from examiner, no eye contact, refusal to take food or drink when offered). Using this diagnostic tool, prevalence of catatonic syndrome appears to be close to 8% of psychiatric admissions. Other signs are also common but less specific: staring, ambitendance, iterations, stereotypes, mannerism, overactivity/excitement, impulsivity, combativeness. Some authors complete this description by adding an affective dimension which is considered specific. Clinical forms are differentiated according to evolution: acute, chronic and periodic forms exist; and symptomatology: excited catatonias have a best prognostic than retarded catatonias. Malignant catatonia is the most studied form because of its severity and high rate of mortality (25%); catatonic patients develop autonomic disturbances with labile blood pressure, hyperthermia, diaphoresis, etc. Malignant catatonia requires ECT intervention in emergency. While catatonias due to general medical conditions are well admitted (first concerned are neurologic etiologies) and concern 14,1% of catatonias, psychiatric comorbidity remains a problem. The documented decline in the proportion of patients with schizophrenia diagnosed as catatonic is congruent with the fact that most studies highlight the strong association between catatonia and mood disorders. However, customary clinical practice continues to over value diagnostic of schizophrenia because catatonic symptoms are recognized as schizophrenic and schizophrenia corresponds to a pharmacological target. Other authors stress that on average 20 to 40% of catatonias are idiopathic. Conceptual proximity between catatonic symptomatology and extrapyramidal syndrome could give some ways for neurobiological grasp of the trouble; mesolimbic and mesostriatal dopaminergic imbalance in a frontal lobe-basal ganglia-brainstem system is supposed to be involved. Treatment procedure could be standardized as follows: 1) Withhold neuroleptic medication. Those drugs are proven to be lethal when catatonic symptoms are developed; 2) Investigations to exclude treatable physical disorders (including standard blood laboratory tests, urinary drug screening, electroencephalogram and brain computerized tomography); 3) Trial of lorazepam. This therapeutic is safe and 80% effective. We propose to administer an initial oral 2,5 mg challenge; catatonic signs are rated after the first hours. If necessary, the patient could receive 3 mg/day with a 6-day full dose treatment and then, treatment would progressively be reduced; 4) If the patient failed to respond to lorazepam, ECT are needed; 5) Earlier use of ECT is recommended if autonomic instability or hyperthermia appears and malignant catatonia is suspected. In conclusion, catatonia has always had an unstable and blurred place in the psychiatric nosography since its first description. It has been incorporated within the group of schizophrenias and underdiagnosed for a long time, but has been predominantly associated with mood disorders for the last ten years. Psychopathological considerations, particularly on cognitive and affective status of catatonic patients, should clarify the nosologic discussion.