[Failure to draw up medical certificates increase judiciary releases]. / La moindre argumentation des certificats médicaux accroît le risque de mainlevée.

OBJECTIVES: In France, a systematic control of compulsory psychiatric admissions has existed since the enactment of the law of July 5th 2011. The Court of Cassation clarified that the liberty and custody judges (JLD) cannot supersede the medical opinion described in the medical certificates. In 2015, the JLD ordered the release of 8.4 % of all compulsory psychiatric admissions. The goal was to compare the quality of medical certificates derived from judicial release based on medical grounds with non-released witnesses from the cohort of compulsory psychiatric admissions ordered in the Groupe Hospitalier Universitaire Paris Psychiatrie & Neurosciences (GHU-Paris) between November 1, 2017 and October 31, 2018. METHODS: We included as cases all the medical certificates derived from judicial release based exclusively on medical grounds from the release cohort of the GHU-Paris from November 1, 2017 to October 31, 2018, concerning the systematic control 12 days after compulsory psychiatric admissions. A witness whose compulsory care had been maintained was matched according to the same judge, place and date of hearing, mode of compulsory care and site of hospitalization. Each certificate was analyzed according to a reading grid relating to the good decisions in matters of compulsory admission and medical certificates' redaction. An overall score, based on the description of the clinical and symptomatic evolution, the level of discernment, the capacity of consent and the mode of compulsory care was awarded to each certificate. RESULTS: Seventeen release files were included in the comparative study. Globally, the clinical progression, psychiatric symptoms, level of consciousness and ability to consent did not differ in the two groups. The grade of quality of certificate was lower in case of withdrawal (2.92±1.08 VS 3.28±0.88, P=0.026). Psychiatric symptoms in "justifiable notice" (the last medical certificate prior to the judicial hearing) were less specified in case of withdrawal (58.8 % VS 94.1 %, P=0.015). Not describing any symptoms led to a 12.51 risk of withdrawal (95 % CI=[1.16; 135.19], P=0.038). Even with witness certificate, clinical progression was noticed in only 85.3 % of cases, in 89.3 % of psychiatric symptoms, in 68.0 % of level of consciousness and 80.0 % for the ability to consent. CONCLUSIONS: Judiciary releases of compulsory psychiatric admissions exclusively based on medical grounds are not arbitrarily decided by the JLD but are based on a failure to draw up medical certificates. Doctors must comply with a careful drafting of all medical certificates: description of symptoms, clinical course, level of consciousness and ability to consent. It is necessary to be attentive to judiciary releases based on medical grounds to evaluate and improve medical practices concerning the drafting of medical certificates.

[Psychiatric emergencies and sense of urgency occurring upstream from health services: What should be done?] / L'urgence psychiatrique et le sentiment d'urgence hors des urgences : que faire en amont des services ad hoc ?

The French psychiatric health system is not properly organized for managing the sense of urgency felt in critical situations that occur upstream from psychiatric health services, in "inappropriate" locations (e.g. home, street, work.), particularly for patients who are unwilling to cooperate and receive health care. Emergency services, police departments, or psychiatric teams - who should take charge? Families are distraught. The authors draw the line to propose a comprehensive and coherent model. Pressing emergencies require the intervention of emergency services, who may, when necessary, receive remote counsel from psychiatric health professionals. Other situations require a quick but delayed access to specialized care, including at-home care. With this comprehensive model, the authors address both a pre-hospital emergency occurring out of a dedicated sanitary place, as well as access to care for patients who are unwilling or partly unwilling to receive health care.

[Descriptive study of the releases pronounced by the liberty and detention judge at groupe hospitalier universitaire Paris psychiatrie & neurosciences from November 2017 to October 2018]. / Étude descriptive des mainlevées prononcées par le juge des libertés et de la détention au groupe hospitalier universitaire Paris psychiatrie & neurosciences du 1er novembre 2017 au 31 octobre 2018.

OBJECTIVE: In France, a systematic control of compulsory psychiatric admissions has existed since the enactment of the law of 5 July 2011. In 2015, the judge of freedoms and detention ordered the withdrawal of 8.4 % of the compulsory psychiatric admissions. The aim of the study is to describe the grounds for judiciary withdrawals of compulsory admissions ordered in the groupe hospitalier universitaire paris psychiatrie & neurosciences (GHU-Paris) between November 1, 2017 and October 31, 2018. METHODS: All of the withdrawal decisions adjudged during the mentioned period in the GHU-Paris were analysed following a specific framework. The main analysis deals with the classification of the "administrative", "medical", and "mixed" grounds. The secondary analysis looks at the fundamental facts affecting the judge of freedoms and detention's decision. RESULTS: Of the 127 orders decided by 21 judges of freedoms and detention analysed in this study, the majority were part of the systematic control of compulsory psychiatric admissions (74.8 %) and were made through a referral procedure by the director's hospital (69.3 %). The main reasons for withdrawal decisions were "mixed" (52.9 %), among which were described: failure to respect time limit (20.2 %), failure to inform the patient (11.6 %), third party's proceeding (8.7 %) and lack of documents (8.7 %). "Medical" grounds account for 31.8 % of all grounds. More precisely, failure to respect the required elements for involuntary admissions in psychiatric services was the greatest subcategory (29.5 %). "Other" grounds represented 15.8 %. No "administrative" ground was found. Judges ordered 69.3 % withdrawals within 24 hours to allow community treatment orders to be put into place. In the centre hospitalier Sainte-Anne, 70.8 % of the 24 appeals quashed the first decision by the judge of freedoms and detention. CONCLUSION: Several reasons justify withdrawals of compulsory psychiatric admissions. Scrupulously respecting procedures and drafting psychiatric certificates might decrease the number of withdrawals.

[Characteristics of patients who received an indication of involuntary admission, with or without the involvement of a third party, in a Parisian psychiatric emergency unit]. / Caractérisation d'une population de patients hospitalisés sous contrainte en ASPDT/u et ASPPI à partir d'un service d'urgence psychiatrique parisien.

BACKGROUND: The French mental health law, first enacted on July 5, 2011, introduced the possibility of psychiatric commitment in case of extreme urgency (imminent peril - ASPPI). The decision of involuntary admission can then be made by the hospital director based on a medical certificate, without the need of a third party request. This procedure was intended to be applied on an exceptional basis, but its use is steadily increasing against the other types of involuntary care. Our study aimed at comparing the characteristics of patients who had received an indication for involuntary admission due to imminent peril (ASPPI) or at the request of a third party (ASPDT/u) in a psychiatric emergency ward, according to sociodemographic and clinical characteristics and regarding the potential implication of a third party. METHODS: An observational study was conducted among patients from the Centre Psychiatrique d'Orientation et d'Accueil (CPOA), located at Sainte-Anne hospital in Paris, from August 1st to 31st, 2016. RESULTS: One hundred and fifty patients with an indication for involuntary commitment were included, 101 of whom for ASPDT/u (67 %) and 49 for ASPPI (33 %). For more than half of the patients from the ASPPI group, a third party had been identified with (39 %) or without (17 %) contact information. Compared to ASPDT/u patients, ASPPI individuals were more socially vulnerable, showed more negligence, and had a lower mean functioning score. The indication for ASPPI status was also associated with behavioural quirks, prior psychiatric hospitalization (especially as an ASPPI patient) and with the diagnosis of chronic psychosis instead of mood disorder. CONCLUSION: Our exploratory results help to better understand how the ASPPI procedure is used in psychiatric emergency wards six years after enactment of the law. They highlight the differences between ASPPI patients and ASPDT/u and raise ethical issues regarding involuntary psychiatric care.

[Long and short stays under ASPPI: Comparison of clinical and non-clinical data from 250 initial certificates]. / Séjours courts et longs en ASPPI : comparaison des données cliniques et extracliniques issues de 250 certificats initiaux.

BACKGROUND: On July 5, 2011, France introduced a law permitting the involuntary admission of patients considered to be in "imminent danger" into psychiatric care without the consent of the family. This is known as "admission en soins psychiatriques pour péril imminent"(ASPPI). ASPPI authorizes all physicians to hospitalize a patient without his or her consent nor the consent of a third party. This differs from previous measures as only one certificate is needed. The law also requires involuntarily admitted patients to present themselves before a judge specialized in Liberties and Detentions (juge des libertés et des détentions), 12 days following their admission. Although there has been an increase in the number of ASPPI admissions when compared to other types of involuntary admission, patients admitted by ASPPI have been hospitalized for a shorter time than others. Some authors, however, have pointed out that decision criteria are frequently interpreted in a loose manner by physicians. This study was conducted at Sainte Anne hospital in Paris. OBJECTIVE: This study tried to determine if there were different clinical and non-clinical characteristics associated with the length of hospitalization under ASPPI. METHODS: This study analyzed all administrative files for patients admitted under ASPPI from January 1, 2015 to December 31, 2015. These files contained the medical certificates and the court orders. The sample was split into two groups: patients hospitalized for a shorter stay and who did not present themselves to the judge and patients hospitalized for a longer stay and who did present themselves to the judge. The certificates were analyzed with a criteria grid, which includes clinical and non-clinical items. Clinical items were taken from the French High Authority of Health (Haute Autorité de Santé) 2005 recommendations. These include suicidal risk, risk to others, drug abuse, delusions or hallucinations, mood disorder and lack of selfcare. Non-clinical items include other information found in the certificate and sociodemographic information found in the administrative file. RESULTS: Among the 250 certificates analyzed, 172 (68.8%) were associated with a long stay and 78 (31.2%) with a short stay. A bivariate analysis found no significant differences between the two groups for non-clinical characteristics and for drug abuse and mood disorder. When no suicidal risk was present, the stay was short in 21% of the certificates and long for 79%. When a suicidal risk was present the stay was short in 43% of the certificates and long for 57% (P=0.0002). When a risk to others was present the stay was short for 19% of the certificates and long for 81% (P=0.003). When delusions and hallucinations were present the stay was short in 15% of the certificates and long in 85 % (P=5×10e-14). When a lack of selfcare was present the stay was short in 10% of the certificates and long for 90% (P=0.01). CONCLUSION: This study identified two types of situations linked with the length of hospitalization for patients under ASPPI. In one situation, associated with a longer stay, we found acute psychiatric disorders exhibited by more delusions, hallucinations, drug abuse, and lack of selfcare. In the second situation, associated with a shorter stay, this study found more episodic situations with suicidal risk. This study suggests that some involuntary admissions could be avoided if physicians could monitor episodic situations in appropriate structures. Moreover the criteria grid we used in this study should be validated to further analyze the quality of the certificates in order to lead to more precise recommendations.

[Study on how schizophrenic patients perceive treatment with injections in the deltoid muscle]. / Étude sur la perception du traitement injectable dans le muscle deltoïde par les patients souffrant de troubles schizophréniques.

UNLABELLED: Despite the advantages of antipsychotic treatments via the injectable route of administration, there are still reservations regarding this type of therapy, notably among health professionals. A survey conducted with patients suffering from schizophrenic disorders revealed the positive opinion that they had of their treatment. Another survey showed that nearly half of the patients preferred an injectable form, and two thirds felt they were cared for better, because of the injectable treatment. The slow release form of risperidone allows a choice between two injection sites: the deltoid muscle or the gluteal muscle. A recent study showed the satisfaction of the health professionals towards this novel form. The survey presented here was aimed at collecting the opinion of patients regarding the possibility of choosing the injection site, and the changes it would make. OBJECTIVES AND METHODS: The survey was carried out by the BVA Institute during the first half of 2011. The interviews with the schizophrenic patients, followed-up as out patients and treated with long lasting antipsychotics (n=281), were conducted face to face at the hospital by BVA interviewers specialised in the field of health, without the presence of any health professionals. A total of 32 centres participated in the survey; 38% of the interviews took place in the Paris area and 62% in various regions. RESULTS: Different dimensions were analysed. (1) The perception of injectable treatment was largely positive: among all the patients, 75% claimed they currently felt better once they had started the injectable treatment. (2) The choice of the injection site appeared important to a majority of patients (70% of the total sample; 79% of patients had experienced both sites of injection), 56% claimed that it was legitimate that they be given the choice and they felt that they were thus able to participate in their treatment (58%), their treatment was more acceptable (54%), and they found that their relationship with the doctor or nurse was enhanced (53%). (3) The preference regarding the injection site went to the deltoid muscle, among those who had experienced both sites. (4) The perception of the injection sites confirms this preference, the positive qualifications often being associated with the deltoid site, and the negative qualifications with the gluteal site. CONCLUSION: The survey presented here could contribute in convincing the health professionals to propose the choice to patients between the two injection sites in order to improve their compliance to treatment. Patients would therefore play a role in the choice of their treatment and hence become more involved in the follow-up.

[Risk of homicide and major mental disorders: a critical review]. / Risque d'homicide et troubles mentaux graves: revue critique de la littérature.

INTRODUCTION: Tragic and high profile killings by people with mental illness have been used to suggest that the community care model for mental health services has failed. It is also generally thought that schizophrenia predisposes subjects to homicidal behaviour. OBJECTIVE: The aim of the present paper was to estimate the rate of mental disorder in people convicted of homicide and to examine the relationship between definitions. We investigated the links between homicide and major mental disorders. METHODS: This paper reviews studies on the epidemiology of homicide committed by mentally disordered people, taken from recent international academic literature. The studies included were identified as part of a wider systematic review of the epidemiology of offending combined with mental disorder. The main databases searched were Medline. A comprehensive search was made for studies published since 1990. RESULTS: There is an association of homicide with mental disorder, most particularly with certain manifestations of schizophrenia, antisocial personality disorder and drug or alcohol abuse. However, it is not clear why some patients behave violently and others do not. Studies of people convicted of homicide have used different definitions of mental disorder. According to the definition of Hodgins, only 15% of murderers have a major mental disorder (schizophrenia, paranoia, melancholia). Mental disorder increases the risk of homicidal violence by two-fold in men and six-fold in women. Schizophrenia increases the risk of violence by six to 10-fold in men and eight to 10-fold in women. Schizophrenia without alcoholism increased the odds ratio more than seven-fold; schizophrenia with coexisting alcoholism more than 17-fold in men. We wish to emphasize that all patients with schizophrenia should not be considered to be violent, although there are minor subgroups of schizophrenic patients in whom the risk of violence may be remarkably high. According to studies, we estimated that this increase in risk could be associated with a paranoid form of schizophrenia and coexisting substance abuse. The prevalence of schizophrenia in the homicide offenders is around 6%. Despite this, the prevalence of personality disorder or of alcohol abuse/dependence is higher: 10% to 38% respectively. The disorders with the most substantially higher odds ratios were alcohol abuse/dependence and antisocial personality disorder. Antisocial personality disorder increases the risk over 10-fold in men and over 50-fold in women. Affective disorders, anxiety disorders, dysthymia and mental retardation do not elevate the risk. Hence, according to the DMS-IV, 30 to 70% of murderers have a mental disorder of grade I or a personality disorder of grade II. However, many studies have suffered from methodological weaknesses notably since obtaining comprehensive study groups of homicide offenders has been difficult. CONCLUSIONS: There is an association of homicide with mental disorder, particularly with certain manifestations of schizophrenia, antisocial personality disorder and drug or alcohol abuse. Most perpetrators with a history of mental disorder were not acutely ill or under mental healthcare at the time of the offence. Homicidal behaviour in a country with a relatively low crime rate appears to be statistically associated with some specific mental disorders, classified according to the DSM-IV-TR classifications.

[Neuroleptic malignant syndrome and atypical antipsychotics: a brief review]. / Antipsychotiques atypiques et syndrome malin des neuroleptiques : brève revue de la littérature.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is an uncommon, but potentially life threatening complication of neuroleptic drugs. In 1960, Delay et al. [Ann Med Psychol 118 (1960) 145-152] described the "syndrome akinétique hypertonique"(hypertonic akinetic syndrome) and its cardinal symptoms: hyperthermia, extrapyramidal symptoms, altered mental status and autonomic dysfunctions. The syndrome often develops after a sudden increase in dose of neuroleptic medication or in states of dehydration. The frequency of NMS with conventional neuroleptic drugs ranges from 0.02 to 3.3%. The pathophysiology of NMS is not clearly understood. It has been suggested that the potential to induce NMS of neuroleptics is parallel to the potency of dopamine blockade in the nigrostriatal tract, mesocortical pathway and hypothalamic nuclei. It is, however, intriguing that NMS may appear with atypical antipsychotics (AA) and especially clozapine (CLZ), which is mainly characterized by its low affinity to D1 and D2 receptors. OBJECTIVE: The purpose of this study was to review cases of NMS induced by AA agents reported in the literature and to discuss the pathophysiology of this complication. METHODS: Cases of NMS related to AA were collected by means of a MEDLINE literature search between January 1986 and June 2005. As key words we used: (NMS and AA), amisulpride (AMS), clozapine (CLZ), olanzapine (OLZ), risperidone (RIS), quetiapine (QTP), ziprazidone (ZPS) and side effects. For the purpose of our review, all cases were critically examined against standard NMS diagnostic criteria according to DSM-IV. Cases involving a coprescription of classical neuroleptics were excluded. RESULTS: Our search yielded 47 cases (eight women, 39 men) of NMS associated with AA meeting DSM-IV criteria. Patients' mean age was 37 years, primary patient diagnoses were schizophrenia (n=26), schizoaffective disorder (n=9), bipolar disorder (n=3), mental retardation (n=4) and other diagnoses (n=5). Drugs involved were: CLZ (n=12), OLZ (n=18), OLZ and CLZ (n=1), OLZ and RIS (n=1), RIS (n=11), RIS and CLZ (n=2), QTP (n=3) and ZPS (n=1). No cases were reported with AMS. Twenty-nine of these 47 patients treated with AA received no other concomitant psychotropic medications; the remaining 18 patients received respectively, benzodiazepines (n=5), Valproate (n=5), lithium (n=4) and antidepressants (n=4). A lethal evolution occurred in two patients receiving in one case olanzapine, risperidone in the second, at a normal dose range. CONCLUSION: Our review indicates that atypical antipsychotics can cause NMS even when prescribed in monotherapy. The occurrence of NMS when prescribing AA and especially CLZ is, however, intriguing, given its low potency to block D2 receptors. This indicates that a low extrapyramidal syndrome-inducing potential does not prevent NMS and suggests the possible role of serotoninergic and noradrénergic receptors in the pathophysiology of NMS.

[Folie à deux: update of an old concept regarding two cases]. / Folie à deux: actualités d'un concept ancien, à propos de deux cas.

INTRODUCTION: Folie à deux or induced delusional disorder is a rare mental disorder. It was initially described by the French Lasègue and Falret in 1877. Two subjects, who live in a close relationship, in isolation, share delusional ideas based on the same themes. Various classifications exist. Its epidemiology remains unclear, because most of the data have been extrapolated from case reports. CASE REPORTS: In this paper, we describe and comment two cases of shared paranoid disorder: in the first case report, a husband shares the paranoiac delusion of his wife; the second case report describes a shared paranoid disorder between a schizophrenic daughter and her mother. LITERATURE FINDINGS: A review of the existing literature is also presented. Some clinical characteristics arise, such as frequent mother-daughter associations and diagnosis of schizophrenia in inducing subject. Particular social and psychopathological conditions for the occurrence of a shared delusional disorder are described, such as personality traits and genetic influences. This article also reviews some forensic issues, which may be of importance, since this disorder is underdiagnosed. Data concerning the principles of its treatment are sparse, but most authors consider that the separation of the two subjects has to be the basis of any intervention. The inducing subject has to be treated with specific medical interventions, including the prescription of antipsychotics. Sometimes, the separation is enough to eliminate the delusional ideas from the induced subject, who, according to the ICD-10 and DSM-IV, is the only one to meet the criteria for shared delusional disorder. The case reports are discussed in light of the review, and some propositions for their treatment are made. CONCLUSION: As shared delusional disorder is a rare disease, only few data exist on its pathophysiology and mechanisms, and controlled studies are needed in order to understand its specific implications better and to define recommendations for its management.

[Comparative evaluation of quality of life in patients with schizophrenia treated with conventional versus atypical neuroleptics: results of a transversal study]. / Evaluation comparative de la qualité de vie de patients schizophrènes traités par neuroleptiques classiques et neuroleptiques atypiques: résultats d'une étude transversale.

AIM: The World Health Organization has defined quality of life as "the perception of an individual, his/her place in life, in the context of the culture and the system of values in which he/she lives and in relation to his/her objectives, expectations, standards and concerns". The quality of life of the schizophrenic patients has been largely studied for the evaluation of their medical, social and therapeutic needs. The impact of neuroleptics, in particular atypical neuroleptics, on the subjective quality of life of these patients remains to be specified. The aim of this study was to compare the subjective quality of life of schizophrenic patients treated with classical neuroleptics (CN) or atypical neuroleptics (AN). METHODS: One hundred patients meeting DSM IV criteria for the diagnosis of schizophrenia (American Psychiatric Association, 1994) were included in the study. Sixty-four schizophrenic patients were treated with CN and thirty-six with AN. The symptomatology of the patients was assessed using the Positive And Negative Syndrome Scale, (PANSS, Kay et al., 1987) and the Schedule for the Deficit Syndrome (SDS, Kirkpatrick et al., 1989). The extra-pyramidal symptoms were assessed using the Extrapyramidal Symptom Rating Scale (Chouinard et al., 1980). The Subjective quality of life was studied using the Lehman Quality of Life Interview (QOLI, Lehman, 1988) translated and validated in France. RESULTS: The patients treated by CN did not differ from the patients treated by AN in terms of severity of the positive and negative symptoms. The patients treated with AN presented significantly less extrapyramidal side effects than the patients treated with CN. No significant difference in terms of quality of life was found between both groups of patients. CONCLUSION: The kind of neuroleptic (CN vs AC) does not seem to influence the quality of subjective life of schizophrenic patients.

Peri-pubertal maturation after developmental disturbance: a model for psychosis onset in the rat.

Schizophrenia is thought to be associated with abnormalities during neurodevelopment although those disturbances usually remain silent until puberty; suggesting that postnatal brain maturation precipitates the emergence of psychosis. In an attempt to model neurodevelopmental defects in the rat, brain cellular proliferation was briefly interrupted with methylazoxymethanol (MAM) during late gestation at embryonic day 17 (E17). The litters were explored at pre- and post-puberty and compared with E17 saline-injected rats. We measured spontaneous and provoked locomotion, working memory test, social interaction, and prepulse inhibition (PPI). As compared with the saline-exposed rats, the E17 MAM-exposed rats exhibited spontaneous hyperactivity that emerged only after puberty. At adulthood, they also exhibited hypersensitivity to the locomotor activating effects of a mild stress and a glutamatergic N-methyl-D-aspartate receptor antagonist (MK-801), as well as PPI deficits whereas before puberty no perturbations were observed. In addition, spatial working memory did not undergo the normal peri-pubertal maturation seen in the sham rats. Social interaction deficits were observed in MAM rats, at both pre- and post-puberty. Our study further confirms that transient prenatal disruption of neurogenesis by MAM at E17 is a valid behavioral model for schizophrenia as it is able to reproduce some fundamental features of schizophrenia with respect to both phenomenology and temporal pattern of the onset of symptoms and deficits.

Necrotizing enterocolitis after antipsychotic treatment involving clozapine and review of severe digestive complications -- a case report.

A case of necrotizing enterocolitis in a 19-year old man treated for schizophrenic disorder, induced by a drug association involving clozapine and requiring surgical treatment, is presented. To our knowledge only few reports have described the occurrence of this complication with atypical antipsychotics. Evidence for linking this complication to clozapine was reinforced by the absence of any viral or bacterial infection. The authors present a review of similar cases, stress the potential hazards induced by such drug combinations and discuss supposed mechanisms of this enterocolitis.

[Treating a manic episode: theoretical guidelines and practice]. / Traiter l'accès maniaque: théories et pratiques.

Theoretical guidelines on the biological treatment of a manic episode differ noticeably from everyday practice, especially in Europe. International guidelines stress the importance of monotherapy, either with lithium, anticonvulsive or antipsychotic agents, depending on the authors and the clinical picture. In some situations, it is recommended to associate an antipsychoticagentanda mood-stabilizer. In the last decade, antipsychotic agents have been mentioned more and more in these guidelines, while lithium has declined in importance. Respective characteristics and specific indications of the different antipsychotic agents have not been fully elucidated yet; nevertheless, some of these have been studied more than others. In practice the situation is quite different, polytherapy is frequent, including classical neuroleptic agents, and for periods that far exceed the duration of a manic episode, despite side-effects and contra-indications particularly frequent in this population. There is no evidence supporting the use of these agents either in the treatment of a manic episode or in the subsequent prophylaxis, but theoretical recommendations do not always reflect the practical situations. Taking this into account and in particular evaluating indications and conditions of polytherapy are critical issues in future studies on the biological treatment of a manic episode; however methodological problems are complex.

Working memory deficits in adult rats after prenatal disruption of neurogenesis.

We investigated the cognitive consequences of a prenatal injection of the mitotic inhibitor methylazoxymethanol (MAM) into pregnant rats at embryonic day 15 (E15) or 17 (E17). The male offspring were tested when adult on a version of the radial-arm maze task that assesses spatial working memory with an extended delay, where performance is dependent, in part, on the hippocampal-prefrontal circuit. A major impairment of spatial learning was observed in E15 MAM rats. However, the E17 MAM rats did learn the rule but were impaired selectively in the 30-min delay-interposed task. Morphologically, the E15 MAM rats exhibited dramatic gross brain abnormalities, whereas the E17 MAM animals displayed aberrant cell migration in the hippocampus and a disrupted laminar pattern in the neocortex. These results suggest that late gestational MAM injection (E17) causes a cognitive impairment in a prefrontal cortex-hippocampus-dependent working memory task. This approach could provide a new developmental model of disorders associated with working memory deficits, such as schizophrenia.