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Although lithium is widely used in current practice to treat bipolar disorder (BD) and treatment-resistant major depressive disorder (MDD) among older adults, little is known about its efficacy and tolerability in this population, which is generally excluded from randomized clinical trials. The objective of this study was to evaluate the efficacy and tolerability of long-term use of lithium among older adults with BD and MDD.Data from the Cohort of individuals with Schizophrenia and mood disorders Aged 55 years or more (CSA) were used. Two groups of patients with BD and MDD were compared: those who were currently receiving lithium versus those who were not. The effects of lithium on psychiatric (i.e., depressive symptoms severity, perceived clinical severity, rates of psychiatric admissions in the past-year), geriatric (overall and cognitive functioning) and physical outcomes (i.e., rates of non-psychiatric medical comorbidities and general hospital admissions in the past-year) were evaluated. All analyses were adjusted for age, sex, duration of disorder, diagnosis, smoking status, alcohol use, and use of antipsychotics, antiepileptics or antidepressants.Among the 281 older participants with BD or MDD, 15.7% were taking lithium for a mean duration of 12.5(SD = 11.6) years. Lithium use was associated with lower intensity of depressive symptoms, reduced perceived clinical global severity and lower benzodiazepine use (all p 0.05), without being linked to greater rates of medical comorbidities, except for hypothyroidism.Data were cross-sectional and data on lifetime history of psychotropic medications was not assessed.Our results suggest that long-term lithium use may be efficient and relatively well-tolerated in older adults with BD or treatment-resistant MDD.

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by difficulties in communication and social interactions as well as by restricted and repetitive patterns of behavior and interests. They are frequently associated with motor signs. However, literature concerning these motor anomalies remains scarce when it comes to the adult population. Among motor aspects, those concerning manual motor skills warrant a particular attention as their alteration often persists through adulthood with a major impact on functioning and quality of life. The purpose of this article was to systematically review and analyze the literature on sensorimotor aspects and manual motor impairments in ASD.We have searched the Medline database using the Pubmed search engine and retaining all articles published since the year 2000 with either their title, abstract or key-words containing the root autis* and any combination of the following terms: hand, manual, finger, dexterity, prehension, grip or grasp. Reference lists where also reviewed. After irrelevant articles were excluded, 33 studies were retained for this work.The basic motor anomaly in autism seems to be a deficit in sensorimotor integration. The central nervous system of individuals with ASD seems unable to efficiently extract sensory information and integrate it correctly into a motor plan and execution. This type of online correction aims to save time on the initial ballistic phase of a movement. Thus, its alteration results in generalized slowness and motor clumsiness that require retroactive feedback corrections. Moreover, difficulties in integrating external sensory information to correctly adapt movement to environmental requirements could explain stereotyped and inflexible behaviors characteristic of autism. The same sensorimotor alterations are found in both gross and fine manual dexterity tasks. They seem to persist significantly though adolescence and into adulthood. To explain these anomalies, the underlying neuroanatomical and neurofunctional substratum might be a hypoconnectivity within cortico-cerebellar tracts. However, several other cerebral structures are also implicated. A delay in the maturational processes of these structures appears to be the common determinant of motor signs found in ASD but also in neurodevelopmental disorders as a whole.Current works tackling motor aspects in autism comprise several limitations preventing homogenization of their findings. Firstly, characterization of the extremely diverse clinical forms of ASD does not always rely on the same clinical criteria or tools. Furthermore, the motor tasks and the clinical assessments used are not always the same across publications complicating comparison. Moreover, sample sizes are almost always small and only a few studies have addressed motor impairments in adults with ASD. Furthermore, only two studies examine the dynamic longitudinal evolution of motor aspects from childhood to adult age. Finally, despite a recent effort of a consistent number of publications converging towards the hypothesis of a deficit in sensorimotor integration, a common pathophysiological model explaining these deficits in ASD is lacking. A more precise description of these motor signs and further comprehension of the neurological mechanisms underpinning them would allow more tailored managements directed towards subgroups with more homogenous neurodevelopmental profiles.

IntroductionHashimoto encephalopathy (HE) is an uncommon syndrome associated with Hashimoto thyroiditis. The relationship between these entities is unclear. Even being rare, it appears to be underrecognized.ObjectivesReport a case of an atypical presentation of psychosis in a patient with elevated serum levels of antithyroid antibodies and review the literature about similar situations.MethodsAccess clinical process, research PubMed, using the mesh terms “Hashimoto encephalopathy” and “psychosis”.ResultsA 21-year-old Portuguese female was conducted by authorities to our emergency department after she called for help and was spotted walking barefoot on the streets. Throughout clinical course she presented persecutory ideas, thought blocks, auditory hallucinations, soliloquies, perplexity, total insomnia, bizarre behaviors like coprophagia, trichotillomania and self-injured burns. After some tests, it was found that the patient had high serum levels of antithyroid peroxidase antibody (TPO) and antithyroglobulin antibody (TGO) and reduced folic acid, without other changes. Trials with corticosteroids showed clinical improvement for short periods, as with antipsychotics. No consistent remission was achieved with either approaches.ConclusionHE is an uncommon syndrome presenting with high titers of antithyroid antibodies that may preconize an acute state of atypical psychosis. Usually, it responds to corticosteroids and so, has a generally good prognosis when treated accordingly. Evidence suggests that HE is an autoimmune disorder instead of thyroid disease.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

A one-pot allylation and hydrostannation of alkynals where the tin byproduct formed in the first step of the reaction is recycled and used in the second step of the sequence is presented. Specifically, a BF3·OEt2-promoted allylstannation of the aldehyde moiety in the alkynal is followed by the introduction of polymethylhydrosiloxane (PMHS) and catalytic B(C6F5)3, which convert the tin byproduct of the allylation into Bu3SnH, which then hydrostannates the alkyne in the molecule. (119)Sn and (11)B NMR data suggest an organotin fluoride species is formed during the allylation step and involved in the tin recycling step.

La rehabilitation psychosociale (RPS) tend a se deployer actuellement en France. Elle accompagne et propose aux usagers en psychiatrie des parcours de soin et de vie menant au retablissement. La RPS doit etre proposee des les premiers troubles psychiques et premier acces au soin, pour de la prevention (Amado, 2018) et pour du soin pour les pathologies confirmees (Franck, 2018). La RPS doit se voir proposee tant dans la schizophrenie, que dans l’autisme ou pour les pathologies neurodeveloppementales complexes, chez l’enfant ou l’adulte. Les parcours en RPS doivent etre personnalises, pour le choix et les techniques a prioriser et pour les outils de la rehabilitation qui dependent du profil du sujet. Parmi ces outils, la remediation cognitive (RC) occupe une place de choix. Elle delivre des programmes adaptes au profil cognitif des usagers, personnalises depuis l’evaluation multidisciplinaire initiale jusqu’au tâches a domicile, renforcees parfois par des case manager, ou par les equipes sectorielles d’adressage, ainsi que par les structures medicosociales d’aval. Ces unites doivent travailler en coordination et synergie avec le centre de rehabilitation, pour une insertion en milieu ordinaire, en milieu protege, ou pour plus d’autonomie et une realisation de soi. Les usagers eligibles pour de la RC doivent etre stabilises, engages pour des programmes longs et couteux intellectuellement, et doivent avoir une esquisse de projet afin que le parcours vers le retablissement prenne sens et constitue un levier de motivation. Nous ne traitons pas une pathologie mais un profil cognitif, premier pas vers une destigmatisation (Amado and Sederer, 2016). Par ailleurs la place de la RC doit s’agencer precisement pour constituer un tremplin, avec un fondu enchaine vers le projet tout proche. Cette dynamique qui prefigure une formation, est un des determinants pour lutter contre la chronicite. En ile de France, l’accent est mis sur les plateformes intersectorielles de proximite, qui se creent selon une logique de deploiement territoriale, suivant une enquete menee a la demande de l’ARS (Moualla et al. 2018). Ces plateformes territoriales de RPS sont aidees et tutorisees par le C3RP, servant de structure support a la dissemination de la remediation cognitive et RPS en ile de France. Plusieurs plateformes ont ainsi vu le jour et d’autres vont suivre. En satellite, des hopitaux de jour et foyers de post-cure orientes vers la RPS creent avec ces plateformes des parcours complexes de RPS pour des pathologies severes, surtout sur Paris et petite couronne. Un groupe de travail Remediation et RPS reunissant les 3 plateformes intersectorielles de RPS des 5 hopitaux du GHT/GHU Paris Psychiatrie Neurosciences, bientot rejointes par les principaux partenaires medicosociaux travaillent depuis bientot trois ans a l’harmonisation des techniques RPS et a l’innovation pour l’insertion pleine et entieres des usagers parisiens en sante mentale. L’ensemble des innovations est aussitot dissemine et diffuse sur le reseau RC et RPS d’ile de France, et sur le territoire national, ainsi qu’a l’international.

IntroductionDisorders of endocrine function are among the most common etiology of psychiatric illness.The link between psychosis and hyperthyroidism is still poorly understood. We report an unusual presentation of hyperthyroidism as a psychotic state. Careful history, physical examination, and laboratory investigation, including thyroid function tests, should be part of the assessment of patients with any unexplained acute psychosis to detect this potentially curable disease. In this way, this article analyzes the psychiatric, physical and laboratory findings associated with hyperthyroidism and treatment.ObjectivesTo report a case of psychosis in a patient with endocrine disease.MethodsClinical records. Research on PubMed and Medscape using the Mesh Terms “hyperthyroidism”, “psychosis” and “thyroid and psychiatric manifestations”.ResultsWe present the case of a male patient, previously followed on our ambulatory psychiatric service for drug-induced psychosis. He was hospitalized due to psychotic symptoms, without substance abuse. Inpatient evaluation diagnosed hyperthyroidism. The patient did not present any somatic changes, except for psychosis. The patient was effectively treated with antipsychotics. He was referred to further evaluation and started antithyroid therapy.ConclusionsThyroid disease should be considered in the differential diagnosis of a broad spectrum of psychiatric symptoms. Psychosis is a rare complication of hyperthyroidism, ranging between 1–20%. The typical psychosis is reported to simulate manic-depressive psychosis. This association reinforces the need of a careful clinical evaluation in patients presenting with psychosis. Such psychiatric symptoms remit successfully with concomitant administration of antipsychotics and normalization of thyroid levels.Disclosure of interestThe authors have not supplied their declaration of competing interest.

El hiperparatiroidismo tiene con frecuencia manifestaciones óseas, de predomínio facial en algunos pacientes. Los autores describen las manifestaciones en una família de la región central de Portugal, como punto de partida para una revisión de los conocimientos sobre esta entidade clínica todavía poco divulgada y que puede tener como primera manifestación la presentación de tumores faciales.Hyperparathyroidism frequently has bone effects. In one subset of patients, these effects involve mainly facial bones (hyperparathyroidism-jaw tumour syndrome). The authors describe an affected family from central Portugal and discuss the features of this still poorly known disease, which can present initially as a facial tumour.

Twenty-three heterocyclic compounds were evaluated for their potential as trypanothione reductase inhibitors. As a result, the harmaline, 10-thiaisoalloxazine, and aspidospermine frameworks were identified as the basis of inhibitors of Trypanosoma cruzi trypanothione reductase. Two new compounds showed moderately strong, linear competitive inhibition, namely N,N-dimethyl-N-[3-(7-methoxy-1-methyl-3,4-dihydro-9H-beta-carbolin-9-yl)propyl]amine (15) and 1,3-bis[3-(dimethylamino)propyl]-1,5-dihydro-2H-pyrimido[4,5-b][1,4]benzothiazine-2,4(3H)-dione (21), with K(i) values of 35.1+/-3.5microM and 26.9+/-1.9microM, respectively. Aspidospermine (25) inhibited T. cruzi TryR with a K(i) of 64.6+/-6.2microM. None of the compounds inhibited glutathione reductase. Their toxicity toward promastigotes of Leishmania amazonensis was assessed.

langage, concentration/vitesse de traitement de l’information, capacites d’abstraction. Des modeles cognitifs ont tente d’integrer ces differentes fonctions pour expliquer les diffi cultes cognitives des patients : ceux-ci rencontrent ainsi des diffi cultes de prise en compte du contexte, des troubles de la planifi cation de l’action, des diffi cultes d’ajustements des plans moteurs et cognitifs, une incapacite de tenir compte des experiences passees, des troubles du monitoring ou de l’initiation de l’action, un defi cit de la theorie de l’esprit, des anomalies conversationnelles, des troubles des interactions sociales, un defi cit de motivation... Ce sont ces diffi cultes qui doivent etre prises en compte lors de la remediation cognitive.

In schizophrenic disorders, supportive psychosocial therapies have been used as adjuncts to pharmacotherapy to help alleviate residual symptoms and to improve social functioning and quality of life. Among these therapies, psychoeducational therapies showed a significant efficacy on improving drug adherence and on reducing relapses. However, according to the French Health Agency, fewer than 10% of psychiatric structures in France offer registered psychoeducation programs. Caregiver apprehension of patients' depressive reactions to the awareness of the disease could underlie the underuse of psychoeducation therapies. Indeed, the psychoeducation programs' impact on objective and subjective quality of life is discussed among the literature. In this context, we conducted a retrospective, monocentric, open-labelled and non-controlled pilot study to measure the impact of a registered psychoeducation program on objective and subjective quality of life of patients suffering from schizophrenia. Secondary objectives included measures of the effects on drug observance and awareness of the disease.We included stabilized patients over the age of eighteen suffering from schizophrenia. Referent psychiatrics were asked to inform the patient of the diagnosis and to prescribe psychoeducation therapy. From 2011 to 2014, we offered three ambulatory programs, each program including fifteen two-hour group sessions. The groups were opened for three to six patients and managed by two caregivers. Themes discussed during the sessions included: schizophrenic disease, treatments, relationships to family, diet, social issues, toxics, relaxation. Objective and subjective quality of life were evaluated one month before and one month after the program using respectively the global assessment functioning (GAF) and the subjective quality of life (SQoL) scales. The Medical Adherence Rating Scale (MARS) and the French IQ8 scale evaluated respectively drug adherence and awareness of the disease. All patients gave their written consent for the study. Based on medical records and scales, we compared data before and after the program using the Wilcoxon test, adapted for small samples.Fourteen patients, with a mean age of 37.6 years, were included. All patients had a chronic antipsychotic treatment and four benefitted from a bitherapy with a mood stabilizer. The mean length of disease was 15.3 years, with a mean number of 3.4 hospitalizations before inclusion. The participation rate was nearly twelve sessions out of fifteen. Mean GAF score before the program was 48/100. After the program, mean GAF score was significantly increased to 54/100 (P=0.008). As to SQoL score, we found a significant difference of the sub item psychological well-being from 3.2/5 before the program to 3.8/5 after the program (P=0.03). Global SQoL score and other sub items (self-esteem, resilience, and physical well-being) showed a slight but not significant improvement. The sub items family relationships and sentimental life were diminished, non-significantly. Concerning the drug adherence, the mean MARS score was significantly increased from 6.1 to 6.4/8 (P=0.03). Comparison of the insight IQ8 scale showed a slight but non-significant increase. When asked to note the program, patients were globally very satisfied, with a mean rate of 8.6/10. Of fourteen patients, one needed to be hospitalized three years after program.This retrospective study on a small sample of patients suffering from schizophrenic disorder pointed out a significant improvement on drug adherence, objective quality of life and psychological well-being, after an eight-month registered program of psychoeducational therapy. These results are in line with a recent report from the Cochrane group who reported a significant raise of GAF associated with psychoeducational therapies. The literature data for subjective quality of life are more contradictory. Despite the small sample and evaluation means that need to be corrected in further studies, we reproduced the results described in the literature regarding the improvement on drug adherence. However, the stability of these effects should be checked in the medium and long term.Adjunctive psychoeducation therapy has a positive impact on reducing relapses in schizophrenia. In this study, we showed a significant benefit on drug adherence, objective quality of life and psychological well-being on a small sample of patients and provide arguments for the development of psychoeducation programs which are currently underrepresented in France. Our results encourage conducting a further prospective multicenter controlled study on a larger sample to clarify the benefit of psychoeducational therapy on objective and subjective quality of life in schizophrenia.

Neurological soft signs (NSS) include anomalies in motor integration, coordination, sensory integration and lateralization and could be endophenotypic markers in autism spectrum disorders (ASD). Their characterization provides a more precise phenotype of ASD and more homogeneous subtypes to facilitate clinical and genetic research. Few scales for NSS have been adapted and validated in children including children with ASD. Our objective was to perform an adaptation to the child of a scale assessing neurological soft signs and a validation study in both general and clinical populations.We have selected the NSS scale of Krebs et al. (2000) already validated in adults. It encompasses 5 dimensions: motor coordination, motor integration, sensory integration, involuntary movement, laterality. After a preliminary study that examined 42 children, several changes have been made to the original version to adapt it to the child and to increase its feasibility, particularly in children with ASD. Then we conducted a validation study by assessing the psychometric properties of this scale in a population of 86 children including 26 children with ASD (DSM 5 Criteria) and 60 typically developing children. Children's ages ranged between 6 and 12 years, and patients and controls were matched for gender, age and intelligence. Patients were assessed using the Autism diagnostic Interview-revised and the Childhood Autism Rating Scale to confirm diagnosis. Typically developing children were assessed using the semi-structured Mini International Neuropsychiatric Interview for Children and Adolescents to eliminate any psychiatric disorder. All children with neurological pathologies (history of cerebral palsy, congenital anomaly of the central nervous system, epilepsy, tuberous sclerosis, neurofibromatosis, antecedent of severe head trauma) and obvious physical deformities or sensory deficits that could interfere with neurological assessment were excluded from the study. Both patients and controls were assessed using the Raven Progressive Matrices to exclude intellectual disability, and the adapted Krebs' scale for the assessment of NSS.Adaptation of the scale consisted of a modification in the order of items, in the use of concrete supports for the assessment of laterality and in the elimination of item constructive praxis. The internal consistency was good with a Cronbach alpha of 0.87. Inter-rater reliability was good, kappa coefficient was greater than 0.75 for 16 items, 3 items had a kappa value between 0.74 and 0.60, only 1 item had a kappa coefficient between 0.4 and 0.59. Good inter-rater reliability was also checked for the total score with a value of intra-class correlation coefficient (ICC) of 0.91. Principal component analysis found five factors accounting for 62.96 % of the total variance. About the comparison between patients and controls, significant differences were found for NSS total score (P=0.000) and all subscores.The adaptation for children of the Krebs et al.' NSS scale proved to be valid, especially in children with ASD.

Objective The principal objective was to compare the effects of milnacipran, an antidepressant characterized by a dual-action on serotonin and noradrenaline reuptake, with placebo on memory, attention and psychomotor performance in healthy volunteers. The secondary objective was to evaluate the effects of milnacipran on mood, anxiety and vigilance in these subjects. Methods In a double-blind crossover randomized trial, milnacipran (50 mg b.d.) or placebo was administered during two periods of 7 days separated by a washout period of 7 days. Memory tests (recall of words, images and coloured bars), tests to evaluate attention and vigilance (squares test, critical flicker fusion test and choice reaction time test) and visual analogue scales for affect and sleep were used. Results There were no significant differences between milnacipran and placebo groups with respect to the psychomotor functions tested. No differences were observed in the Norris scales for vigilance, anxiety or satisfaction or in the sleep questionnaire (sleep latency, sleep quality and waking). Conclusion Milnacipran, administered at 100 mg per day for 7 days to healthy volunteers, had no effects on cognitive functions. Copyright © 2004 John Wiley & Sons, Ltd.

IntroductionThe relationship between brain tumours, temporal epilepsy and psychiatric symptoms are historically known.ObjectivesTo report a case of mania in a patient with previous diagnosis of bipolar disorder, temporal tumour and temporal epilepsy.MethodsClinical records. Research on PubMed, using “lateral temporal epilepsy” or “brain tumour” and “mania”.ResultsA 52 years old man was conducted to the emergency department by the police. He was found with psychomotor agitation at the Sanctuary of Fátima. He was apparently hyperthimic with flight of ideas. He had a history of epilepsy and temporal tumour and two previous manic episodes. It was assumed as a maniac episode.During inpatient evaluation, patient had memory for the occurrence. He described a sudden onset on the day before, after drinking wine. He described delirant atmosphere, persecutory and mystic delusional beliefs “this is the third secret of Fátima being revealed”, followed by ecstasy and psychomotor agitation. Remission was obtained in one week on psychotropics. MRI documented the lesion. Electroencephalography performed one month later revealed “slow waves.”ConclusionsOrganic causes should be excluded before consider a psychiatric disorder. The hypothesis of epilepsy-related psychosis or mania and other effects of a temporal tumour should be considered in etiology. However, co morbidity with bipolar disorder cannot be excluded.Disclosure of interestThe authors have not supplied their declaration of competing interest.

A direct one-pot alkylation-hydrostannation sequence of alkynes having a remote aldehyde substituent is detailed.

The hypothesis of cerebral plasticity in psychiatric disorders has encouraged clinicians to develop cognitive remediation therapy (CRT), a new therapeutic approach based on attention, memory, planning, and mental flexibility tasks. The first cognitive remediation programs were developed and validated for adults with schizophrenia and were shown to have a positive impact on executive functions as well as on quality of life. In children and adolescents, researchers emphasized the existence of executive dysfunction in neurodevelopmental disorders such as autistic spectrum disorder, attention deficit disorder, and eating disorders. For these disorders, neuropsychological studies suggest that memory, planning, attention and mental flexibility are impaired. Despite the paucity of studies on cognitive remediation (CR) in children, preliminary results have suggested, as in adults with schizophrenia, good compliance and optimization of executive functioning. Consequently, programs dedicated to young subjects were developed in English-speaking countries, and the Department of Child and Adolescent Psychiatry of Sainte Anne Hospital (Paris) developed a new CR program for children with attention deficit disorder, academic problems, or eating disorders. These programs complete the field of CRT proposed by Sainte Anne Hospital's Remediation and Psychosocial Rehabilitation Reference Center, initially designed for adults with schizophrenia. Our team used and adapted validated tools such as Delahunty and Wykes's CRT program (translated and validated in French by Amado and Franck) and Lindvall and Lask's CRT Resource Pack. One program was developed for an adolescent with anorexia nervosa and applied to the subject and her family, but the purpose of this paper is to present a CR approach for children with attention deficit disorder or academic disorder, a 6-month program based on paper-pencil tasks and board and card games. The team was trained in different kinds of cognitive remediation, and the program was applied by a clinical nurse with the supervision of a child and adolescent psychiatrist and the department's neuropsychologists. Paper-pencil tasks were adapted from the CRT program for adults; the card and board games used were geometric figures, illusions, Rush Hour(®), Set(®), Jungle Speed(®), Color Addict(®), etc. These games are available in stores and the program can be applied at home, which helps families set aside their preoccupations with their child's academic performance. Diagnostic and neuropsychological evaluations were done before the beginning of the therapy and repeated at the end of the 6-month program. This program does not ignore the metapsychological impact of the therapy, and work on self-esteem is also done. The presence of the therapist is necessary, which seems better than a computer program, which cannot encourage the young subject in the same personalized and empathetic way. We therefore conducted the first clinical feasibility trial of cognitive remediation in young subjects and present a clinical case of a 6-year-old boy with attention deficit disorder and academic disorder. The results of neuropsychological evaluations before and after therapy suggest improvement in executive functions and better self-esteem. Satisfaction for the boy and his family was high. Even if these results need to be replicated, cognitive remediation appears to be a new therapeutic tool, complementary to classical approaches used in childhood psychiatric disorders. The Department of Child and Adolescent Psychiatry will submit this program to a research program conducted by the National Health Department to study the impact of this approach in a controlled study.

The neuropeptide oxytocin (OT) is an evolutionary highly conserved molecule that plays a part in the regulation of complex social cognition and behaviours. From a pathophysiological point of view, several studies have evidenced dysfunctions of the oxytocinergic system in autism spectrum disorders (ASD): a lowering of plasma OT and genetic or epigenetic anomalies of the OT receptor. Therefore, some authors have hypothesized that an abnormality in the OT neurotransmission may account for several features of autism and that a treatment restoring a normal OT pathway functioning could improve social abilities. OT administration has thus been used in clinical trials, especially in groups of subjects suffering from autism. Some studies found that OT decreased repetitive behaviours, enhanced emotional understanding of speech intonation, improved performance of the Reading the Mind in the Eyes Test and reinforced cooperation. Nevertheless, the findings of the OT administration studies on clinical samples show great diversity. The context, the personality and childhood experiences of the subject could be moderators influencing the effect of exogenous OT. Besides, three mechanisms could play a part in the action of OT on ASD social symptoms: anxiety reduction (with a lowering in the hypothalamic-pituitary-adrenal axis responsiveness and in the amygdale reactivity to social stimuli), increased affiliative motivation (involving the dopaminergic pathway and several regions of the social brain) and enhanced perceptual selectivity and social stimuli salience. To conclude, OT could be a promising molecule used as a treatment to promote social behaviours, helping individuals with ASD to develop new relationships. OT could be administered during a cognitive-behavioural therapy to reinforce the efficacy of such procedures. More studies are needed, on larger samples, to investigate the safety and efficacy of OT administration and to specify optimal dosages and characteristics of patients who may benefit from this treatment.

The limited thermal stability of the polycyclic dione 1 can be circumvented by reacting its derivatives, hydroxyketone 3 and diol 4 with tetrachlorothiophene dioxide (6d) to yield the mono-Diels–Alder adduct 8 and rearranged polycyclic ether 11, respectively. The structures of both new products were confirmed by X-ray structure determination.

Les signes neurologiques mineurs (SNM) sont des marqueurs aujourd’hui bien reconnus dans la schizophrénie, présents à un moindre degré chez les apparentés. Leur signification et leur spécificité reste néanmoins incertaines. Des aspects méthodologiques pourraient expliquer certaines de ces incertitudes (échelles variables selon les publications, méthodes de cotation sensible ou non au changement, types de signes pris en comptes etc) [1]. Les corrélats des SNM peuvent apporter des éléments de réponses sur leur origine et leur signification. Nous avons ainsi montré que la SNM sont associés à une moindre performance cognitive, à plus d’erreurs dans les tâches oculomotrices, notamment dans des tâches de saccades adaptatives [2], ainsi à une altération du circuit préfronto cérébelleux [3], suggérant un dysfonctionnement cérébelleux.Par ailleurs, nous avons également montré que les patients ayant des SNM ont une altération de la morphologie corticale, avec une moindre gyrification corticale, témoignant de l’origine développementale des SNM [4].Enfin, nous avons montré récemment que les SNM sont plus marqués chez les sujets présentant un début des troubles précoces, avant l’adolescence (avant 15 ans), comparés à ceux présentant un trouble débutant à l’âge adulte, suggérant à nouveau que les SNM sont les marqueurs d’une forme à charge développementale plus importante.L’association des SNM avec un âge de début précoce et des anomalies structurales touchant en particulier les circuits cérébelleux, suggère que les SNM pourraient permettre d’identifier un sous-type de schizophrénie précoce, et interroge sur un continuum avec les troubles du spectre autistique.

Neurological soft signs (NSS) are subtle neurological abnormalities that cannot be linked to the achievement of a specific region of the central nervous system and which are not part of a particular neurological syndrome. These signs are observed in the case of diseases supporting the neurodevelopmental model such as schizophrenia in general and its early form defined notably by an age of onset of less than 18 years. Indeed, the NSS belong to a set of clinical, cognitive, electrophysiological and neuroanatomical markers reflecting neurodevelopmental brain abnormalities in patients with schizophrenia.The objectives of our study were to determine the prevalence, the scores, and the nature of neurological soft signs (NSS) in adolescent patients suffering from early onset schizophrenia diagnosis in comparison to healthy controls, and to explore the correlations between NSS and the demographic, clinical and therapeutic features of these patients.Twelve adolescents were recruited in the Child Psychiatry Department at the Razi Hospital (Tunisia), with the diagnosis of schizophrenia according to the DSM-IV supplemented by the Kiddie SAD PL. They were matched by age and educational level with twelve healthy controls without psychiatric family or personal history. The clinical status of the patients was assessed using the Positive and Negative Syndrome Scale (PANSS). Neurological soft signs (NSS) were rated with the Neurological Soft Signs Examination (NSSE) by Krebs et al. (2000) for the two groups. This scale is composed of 23 items exploring motor coordination, motor integrative function, sensory integration, involuntary movements and quality of lateralization.The mean age of our population was 14.7 years. The average age of onset of the disease was 12.2 years. The sex-ratio was 1.4. Educational level was 7.4 years. The PANSS mean total score was 74.3. The mean daily dose, in chlorpromazine equivalents, was 523.9 mg/day. Four patients received a strict monotherapy of antipsychotics, while the other patients were receiving an association of two neuroleptics. The prevalence of NSS was 100% (cut-off point=11) with a mean total score of 29.3±4.1. The highest score was for the motor coordination (10.1). As for the control group, the mean total score was 7±1.3. A highly significant difference was found between patients and controls for all sub-scores of NSS. Negative correlations were found in patients, between age and neurological soft signs total score (P=0.05; r=-0.57) and also with sensory integration score (P=0.04; r=-0.58). The NSS total score was also correlated with low educational level (P=0.03; r=-0.61). There was no correlation between neurological soft signs scores and PANSS scores or the daily dose of antipsychotics.The prevalence and NSS scores are high among young people with early onset schizophrenia diagnosis illustrating the existence of structural abnormalities of the brain, themselves consequences of early neurodevelopmental disturbances, which would support the neurodevelopmental hypothesis concerning this pathology.

Teenagers and adults with intellectual disabilities are nowadays "over-handicapped", often due to lack of care in self-sufficiency and continued learning, two essential domains for living in a community. Their cognitive limits, particularly on the executive functions, could be an obstacle to their involvement in the daily life activities, through their difficulties to plan, anticipate, shift and maintain information in working memory. These high level mental functions can be taught with the CRT program (Cognitive Remediation Therapy - Wykes and Reader 2005) developed in other pathologies and providing an adaptation regarding the developmental level of the person.Firstly, it is essential to determine cognitive developmental levels of the teenager or the adult, using standard tools, such as Wechsler scales. Secondly, functional and/or adaptative levels have to be assessed using specific tools, such as the Vineland Adaptative Behavior Scale 2nd Edition (VABS-II, Sparrow et al., 2005) and the Functional Intervention Scale (EFI, Willaye et al., 2005). Finally, in order to clearly distinguish what are the preserved and impaired cognitive domains, standard tools assessing executive functions such as the Wisconsin Card Sorting Test, the Tower of London, Stroop Test and BADS are used if possible for the patient. The setting of cognitive remediation programs, previously developed for schizophrenic patients, requires adaptation for teenagers and adults with intellectual disabilities, taking into account the limitation of their cognitive abilities. In this paper, we will show that the CRT method for cognitive remediation is particularly relevant for subjects with intellectual disabilities. This method is hence focused on strategies and exercises to improve working memory, categorization and moreover executive functions. Of course this method might need adaptations, with examples based on simplification of the different tasks, notably for verbal materials, and with variations of the media used. These sessions will be part of a wider individualized caring project, allowing the person to transfer the cognitive acquisitions to his/her daily life.The use of cognitive programs adapted to people with intellectual disabilities can provide benefits in the development of autonomy and daily life activities, leading to a better quality of life and self-esteem.

Many studies have focused on specific motor signs in autism and Asperger's syndrome, but few has been published on the complete range of neurological soft signs (NSS) in children with pervasive developmental disorder (PDD). Scarce are the studies evaluating NSS in children suffering from PDD not otherwise specified (PDDNOS).This study compared performance of 11 autistic children (AD) and 10 children with PDDNOS, with controls matched on age, sex and cognitive performance on Krebs et al.'s NSS scale. Because of the duration of the assessments and specific difficulties encountered in managing some items, an adaptation of the scale had to be made during a pilot study with the agreement of the author. To be eligible, patients had to meet the following inclusion criteria: an age range of 6-16 years, a diagnosis of autistic disorder or PDDNOS based on the DSM IV criteria (American Psychiatric Association 1994). The autism diagnostic interview-revised (ADI-R) was used in order to confirm the diagnosis and to evaluate the association of the symptoms to the severity of the NSS. The childhood autism rating scale (CARS) was completed for the patients in order to evaluate symptoms at the time of the NSS examination. Cognitive ability was assessed with Raven's progressive matrices. Were excluded patients with: history of cerebral palsy, congenital anomaly of the central nervous system, epilepsy, known genetic syndrome, tuberous sclerosis, neurofibromatosis, antecedent of severe head trauma, Asperger's syndrome, obvious physical deformities or sensory deficits that would interfere with neurological assessment, deep mental retardation and recent or chronic substance use or abuse. Healthy controls shared the same exclusion criteria, with no personal history of neurological, psychiatric disorder or substance abuse, no family history of psychiatric disorder and normal or retardation in schooling. All study procedures were approved by the local Ethics Committee (Comité d'éthique, Razi Hospital), according to the declaration of Helsinki.There was no difference between patients and controls with respect to sex, age and cognitive function. All children had an IQ higher than 81. Significant differences were found between AD children and control group in the motor integration function and sensory integration function. Different NSS scores were significantly higher in the PDDNOS group than in controls: the total scores, motor coordination, motor integration function, sensory integration and abnormal movements. Lower performance in motor coordination skills was associated with higher ADI-R communication score in the AD group. No relationship was found between NSS and CARS' total sore.This study confirms the impaired neurological functioning in autistic as well as PDDNOS children. The association of motor impairment with autistic symptoms highlights the argument that motor control problems can be part of the autism spectrum disorders. The lack of relationship between NSS and intellectual aptitude in the clinical sample provides new elements for the neurodevelopment model of the autism spectrum.

The title compound, C(10)H(8)O(2), is a precursor to an unusual bis-homoaromatic dication and to heterodiamantanes and other oxa-cage compounds. Two independent mol-ecules, each of which is situated on a center of symmetry, comprise the unit cell. Both mol-ecules are in nearly identical chair conformations.

The title compound, C10H12O2, was synthesized as a candidate for further functionalization. The asymmetric unit comprises two independent mol­ecules, both of which are situated on a center of symmetry. Both mol­ecules are involved in a network of hydrogen bonding, with each alcohol group participating in one hydrogen bond as a donor and in a second hydrogen bond as an acceptor.

The title compound, C(10)H(12)O(2), was synthesized as a candidate for further functionalization. The asymmetric unit comprises two independent mol-ecules, both of which are situated on a center of symmetry. Both mol-ecules are involved in a network of hydrogen bonding, with each alcohol group participating in one hydrogen bond as a donor and in a second hydrogen bond as an acceptor.

espanolEl hiperparatiroidismo tiene con frecuencia manifestaciones oseas, de predominio facial en algunos pacientes. Los autores describen las manifestaciones en una familia de la region central de Portugal, como punto de partida para una revision de los conocimientos sobre esta entidade clinica todavia poco divulgada y que puede tener como primera manifestacion la presentacion de tumores faciales. EnglishHyperparathyroidism frequently has bone effects. In one subset of patients, these effects involve mainly facial bones (hyperparathyroidism-jaw tumour syndrome). The authors describe an affected family from central Portugal and discuss the features of this still poorly known disease, which can present initially as a facial tumour.

Electroconvulsive therapy, a standard treatment in mood disorders, is sometimes also indicated in psychotic disorders, especially in the treatment of refractory schizophrenia. In this instance, maintenance electroconvulsive therapy (M-ECT) can also become a long-term treatment. This paper presents the effects of M-ECT in the treatment of refractory schizophrenia using a retrospective analysis. Previous works showed that electroconvulsive therapy is effective on catatonia, anxiety with somatisation, lack of compliance, opposition, delusions especially with hallucinations and persecution, anorexia, agitation, carelessness, aggressive behaviour and moral pain. It is ineffective on bewilderment, somatic complaints and negative symptoms.A retrospective analysis of a clinical cohort of patients treated with M-ECT was carried out to determine the specific indications of M-ECT, its effectiveness on clinical symptoms, quality of life, relapse rates and use of medication. Nineteen patients with DSM-IV diagnosis of paranoid schizophrenia (n=5), schizophrenia with neurotic symptoms (n=3), disorganized schizophrenia (n=1), hebephrenia (n=3) and schizoaffective disorder (n=8), treated in the department of the University Hospital of Sainte-Anne in Paris, received M-ECT between 1991 and 2005. Seven patients are still under this treatment. Their mean age at the beginning of treatment was 47.5 years with a mean duration of the illness of 24 years. The indication of M-ECT was the increase of acute episodes, an increase of symptoms intensity, the inefficiency or intolerance to pharmacological treatments or an early relapse after ECT discontinuation. All patients had previously been successfully treated by ECT during an acute episode. Each patient received an average of 47 bilateral M-ECT under general anaesthesia at one to five weeks' intervals for a mean period of 43 months. All of them were also treated by antipsychotics; in addition, 30% received mood stabilizers and 10% antidepressants. The dosage of antidepressants and mood stabilizers was reduced during M-ECT treatment, especially in patients with schizoaffective disorder, probably in relation with the effectiveness of ECT on mood symptoms.During M-ECT, the mean duration of yearly hospitalizations was decreased by 80% and the mean duration of each hospitalization by 40% with a better ability to take part in activities, sometimes even to return home or go back to work. There was also a positive effect on quality of life considering the severity of symptoms and the long psychiatric history of these patients. The possibility to go from a full time hospitalization to a day-care facility or to live in a halfway house can be considered as a huge progress. M-ECT was efficient on mood symptoms, delusions, anorexia, suicidal impetus, anxiety symptoms and increased cooperation and treatment compliance. Efficacy on obsessive compulsive symptoms was less obvious. There was no effect on dissociation and negative symptoms. Relapses essentially occurred after a stressful life event, a too long interval between the M-ECT sessions or, in 50% of the cases, without any obvious etiology. It required a revision of the M-ECT program and, most of the time, an hospitalization for full ECT treatment.There is no consensus on the rate and number of M-ECT as it varies from patient to patient and depends upon the extent of the clinical response and side effects. The discontinuation of M-ECT will depend on the clinical symptoms, compliance and tolerance to ECT. As it is the case with ECT treatment for an acute episode, available evidence suggests that treatment with antipsychotics should continue during the maintenance ECT course.Maintenance electroconvulsive therapy combined with medication may be an efficient alternative to pharmacological treatment alone in refractory schizophrenia. Alternative therapeutical strategies are crucial in this domain, due to the important public health problem it raises. There are few randomised prospective controlled clinical trials regarding this treatment and further clinical investigations are necessary, notably to define standardized criteria for M-ECT programs.

Most visual environments contain more information than the human brain can process in real time. To overcome this limitation, the attention system acts as a filter by selectively orienting attention to specific regions of the visual field. This ability to orient attention can be reflected in covert shift processes of attention.In a typical covert orienting task, subjects have to maintain fixation on a central cross and respond as quickly as possible to a target, which appears in a peripheral box following a cue that summons attention to the direction where the target is going to appear (valid cueing) or to the contralateral direction (invalid cueing). When the cues are nonpredictive, the response characteristics critically depend on stimulus-onset asynchrony (SOA). With short SOAs (300ms), valid cues result in a reaction time advantage over invalid trials, which is due to a reflexive shift of attention towards the source of stimulation. In contrast, with longer SOAs, valid cues result in longer reaction times to the subsequent target.This phenomenon is known as the inhibition of return and is mostly thought to reflect an inhibitory mechanism protecting the organism from redirecting attention to previously scanned insignificant locations. Many studies have reported blunted or delayed inhibition of return in patients with schizophrenia. However, some authors reported normal amounts of inhibition of return. This can be partly explained by the use of manipulations of the covert orienting of the attention paradigm that is known to enhance the course of inhibition of return.The deficit of inhibition of return seems to be time-stable and to be unrelated to psychopathology or length of illness. The contribution of neuroleptic medication to this deficit cannot be determined. Recent data suggest a deficit of inhibition of return in two human models of psychosis (dimethyltryptamine and ketamine). Further studies should clarify whether blunted inhibition of return might represent a trait marker of schizophrenia.

Previous studies on schizophrenia have suggested that context-processing disturbances were one of the core cognitive deficits present in schizophrenia. Schizophrenic patients have a failure either of inhibition strategy and maintenance of visuospatial information (25) in condition of contextual interference. In the present study, we explored the performances of untreated schizophrenic patients with 2 tasks exploring detection and long term retention of complex visual features and field dependence-independence tasks were selected. These abilities involve temporary maintenance of visuospatial information and executive functioning of visual working memory system. Several studies have shown that cognitive deficit may depend on schizophrenic symptomatology. However results remain controversial in determining the specific influence of negative and positive symptomatologies as well as clinical disorganization. Our goal was to explore the processing of spatial context and its relation to disorganized syndrome. This study was approved by the local ethic committee.Thirty-six schizophrenic patients were included according to DSM IV criteria (19 neuroleptic naïve, 17 unmedicated patients during more than 3 months). Thirty-six healthy controls were matched to patients for age, gender and level of education. Absence of axis 1 pathology was attested for controls with SCID-NP. Current symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) (14). Clinical disorganisation was evaluated with the disorganisation score established upon a factorial analysis of PANSS by Lepine and Lançon. Items selected to distinguish the disorganised group were abstraction, disorganization, orientation, and attention.Two tasks of embedded figures were administered individually to patients and controls. The Faverge task (Research of Figures-RF) (10) evaluates the ability to recognize the target from spatial complex geometrical figures. The Group Embedded Figure Task (GEFT - Oltman) assesses the detection and maintenance of visual target and its recognition within a complex figure. Performance between patients and controls were compared with the Student T test. The comparison of two clinical subgroups of disorganized and low disorganized patients and control group was performed with an ANOVA. Tuckey test was used for pairwise comparisons.We defined two subgroups of patients, disorganized patients (subscore 12, n=17) and low disorganized patients (subscore12, n=19). Theses 2 subgroups were similar for age and level of education. Concerning the two tasks, there was no significant difference between schizophrenic patients and normal controls. The comparison between subgroups of disorganized and low disorganized patients, for RF task, showed a decrease of correct answers with disorganized patients (p0.05). For GEFT task, disorganized patients had a decrease of correct answers p0.01) and more errors (p0.01) and omissions (p0.05). The low disorganized patients exhibited for the two tests comparable performance to controls. The disorganized patients had a decrease of right answers (p0.05) and more errors (p0.05) than controls for GEFT task and no significant difference for RF. However, with IQ (evaluated with an abstract reasoning test) introduced as covariate, only correct answers for GEFT task remain significant (p0.05).The weak performance of disorganized schizophrenic patients for two tasks RF and GEFT showed that treatment of visuospatial information was impaired in the first perceptive phase of selection and in the organization of information (RF), especially with the maintenance of visual information in memory (GEFT). By contrast, low disorganized patients demonstrated a correct analytic treatment of elementary processing and visuospatial working memory.The severity of disorganization influences the visuospatial context processing and visuospatial working memory. These results show the heterogeneity of cognitive functioning regarding to schizophrenic symptomatologies. This difficulty could be related to a problem of central executive functioning in the visuospatial component of working memory, possibly mediated by the dysfunction of dorsolateral prefrontal cortex.

This chapter discusses creative issues relating to the process of digitization in the areas of sound composition, digital photographic work, and Internet-based video art. The authors refer to personal practical and academic experience in the use of computers, digitization and the Internet in the creation, manipulation and distribution of audio, stills and video — in an arts and commercial context.

Behavioural modifications induced by psychotropic drugs results primarily from their pharmacological properties. According to classification of psychotropic drugs, sedative compounds contrast with psychostimulating medications. Behavioural effects of psychotropic drugs depend on dosing, subject's status (patient or healthy volunteer), acute or chronic administration, and environment. Some psychotropic compounds, particularly sedative drugs, decrease the level of mental alertness and cognitive functioning. But those deleterious effects tend to disappear during the course of a repeated administration. Some psychotropic drugs, especially benzodiazepines, induce a tolerance effect, eventually a psychic or a physiological dependence state evidenced by withdrawal reactions. Such similar dependence processes have been reported with other psychotropic drugs. Forensic problems have been attributed to some psychotropic compounds, like benzodiazepines: paradoxical aggressive reactions, psychomotor automatism; Psychotropic drugs usually can confer a positive effect on behaviour owing to their therapeutic action by the way of improving the illness and consequently the life of patients in the cases of depression, anxiety or schizophrenia.

The prevalence rate of transsexualism varies from 1 to 50,000, to 1 to 100,000. Although it remains an infrequent affliction, transsexualism generates usually major suffering and may be responsible of many complications like suicide, self-mutilations, affective disorders and social disabilities. Since the first descriptions of Esquirol in the nineteenth, the medical community has always been questioned on medical, legal, social or ethical aspects of transsexualism. The aetiology of the trouble is still unknown. In the absence of biological marker, the syndrome of transsexualism can be defined only with clinical criteria. The main differential diagnosis are sexual ambiguities and psychotic disorders. For the specialists, satisfying the patients demand of a surgical and social reassignment still remains the only way to improve their clinical condition and avoid the onset of many dramatic complications. Without any treatment, the evolution of the trouble is chronic, without remission. Longitudinal studies of transsexual patients with a five year follow-up demonstrated subjective improvement in two thirds of the patients and don't find either higher rates of suicides nor psychotic decompensations after surgery and hormonotherapy. Clinical and neuropsychological studies of sexually differentiated cognitive abilities of transsexual patients, before and after hormonotherapy, could allow us in improving the understanding of sexual differences of the brain.

Cognitive functions are known to be impaired by ECT. The aim of this study is to differentiate the effects of electroconvulsive therapy on some cognitive functions according to the mode of application of the electrodes. The brief-pulse Thymatron DG apparatus allows to control four electrical parameters and to assess electroencephalographic data. The preliminary sample comprises nine patients suffering of major depressive disorder; they are randomly assigned to the mode of application of the electrodes, bilateral or unilateral to the non dominant hemisphere. Clinical evolution is surveyed by the Montgomery and Asbert Depression Rating Scale. Non mnesic functions are assessed: arousal by CFF (Critical Fusion Frequency), and attentional, motor and decisional abilities by CRT (Choice Reaction Test). Different mnesic function are studied by selective reminding test, cued recall test, block tapping test and picture fragmentation test. After treatment by ECT, verbal mnesic functions assessed by selective reminding test are impaired with the bilateral application. Whereas they are not modified with the unilateral application. The variance of CFF regains a physiological value in the bilateral group, but remains altered in the unilateral.

In this review the authors propose to study the impact of antidepressants on attention, memory and motor functions in healthy volunteers and depressed patients on single and long-term administration. After reviewing the principal cognitive functions, we examine the actual investigation means to conclude that the Critical Flicker Fusion Test (CFFT) is one of the most drug-sensitive tests. It permits a categorization in: sedative antidepressants that in single administration lower CFFT; compounds with no effect on CFFT and no deleterious cognitive effect; and finally substances that raise CFFT and may have psychostimulating properties. On single administration amitriptyline is the most sedative antidepressant on attention or motor level. It seems to produce negative effects on memory level. However, experimental trials give contradictory results. Imipramine in single administration also has sedative effects on memory and car driving capacity. However divergent results of experimental trials do not allow any conclusions of a clearcut negative cognitive effect. Memory impairments with imipramine appear at administration levels of 150 mg. Mianserin has a sedative impact on attention and motor level at low doses (10 mg). Among the tricyclics, nortriptyline has a highly dose dependent sedative effect that has been shown on attention tests (Time Reaction:TR, Digit Symbol Substitution Test: DSST). Among non-tricyclic compounds, doxepine lowers attention and motor performances. Maprotiline (75 mg) lowers CFFT and has a dose dependent effect. Trazodone also has a negative impact on attention tests. Finally viloxazine lowers CFFT but does not impair other attention or motor tests on a 100 mg doses. Buspirone, lofepramine, midalcipran and zimelidine are antidepressants with no effect on CFFT and do not have any positive or negative cognitive effect. On the other hand nomifensine, paroxetine and fluoxetine raise CFFT in healthy volunteers on single administration. Improvement of CFFT performances was found in an isolated manner for nomifensine and paroxetine on 30 mg doses with no other memory or motor effects. MAO-Inhibitors do not impair attention or motor function; thus moclobemide has no negative impact on memory, attention or car driving tests. Cognitive impact of antidepressants in depressive patients seems the same with those of healthy volunteers on single administration. In long-term administration antidepressants have different effects in healthy and depressed subjects. In healthy volunteers cognitive effects of most compounds are normalized after the second week of treatment. However, attention and motor performances with amitriptyline are normalized after 3 weeks of treatment. Sedative motor or cognitive effects of imipramine do not exceed 8 days.(ABSTRACT TRUNCATED AT 400 WORDS)