[Multiphasic time: Representations, modelisation and dynamics: Putting time back in motion after traumatic violence]. / Le temps multiphasique : représentations, modélisation et dynamique: De la remise en mouvement du temps dans les violences traumatiques.

A multiphasic time model, integrating the past, present and future in close interrelations, is first presented and offers a contextual approach to the perceptions and responses of an individual according to his/her personal history and environment. The present and future prospects are in continuity with the past and its consequences and effects. The past, even when it is not or no longer expressed, influences the present and the future, and this over several generations. Past life events and experiences, as well as psychological and biological states previously experienced by the individual (such as emotional states, illnesses, etc.) and his/her previous responses (adaptive or maladaptive responses, leading to failures or successes, etc.) modify, according to the individual' s personal history, his/her current perceptions and reactions to life events and environmental stimuli. In addition, some variables influence a person's current perceptions and reactions such as environmental moderator variables (social, cultural, physical environment), current psychobiological states of the individual (emotions, motivation, etc.), and characteristics of life events and environmental stimuli (depending on whether these life events are, for example, single or repeated, predictable or unpredictable). What matters is less the life event or environmental stimulus in itself, than the individual's perception and reactivity to this event/stimulus according to the context of his/her personal history, as well as his/her current environment and psychobiological state. Moreover, the perception of the present depends not only on the traces of the past but also on our ability to project ourselves into the future and to envision it. Thus, dreams of the future allow one to escape by introducing another temporality allowing a person to disconnect from the present, to create an internal reality replacing the external reality, and to live the present differently. But the memory of the past and the representations of the future are constantly constructed and reconstructed in the present according to the emotions of the individual and his/her environment. Based on the integrative approach proposed in the multiphasic time model, the trace of the past, as well as the dream of the future, contribute to writing the present and influence the future, but the nuances of the present participate also in the reconstruction of past memory and the projection into the future, with interrelationships where all times are closely intertwined in the individual's current representations. By relying on this multiphasic time model, new perspectives for understanding and treating traumatic violence are proposed. Indeed, the representations of time that we construct are sometimes related to the perception of a frozen time that no longer flows, especially after an experience of traumatic violence. The trauma breaks into the psychic life of the individual by causing a rupture, and the perception of time is then altered. Time stops, this is the time of trauma. There is no longer multiphasic time, but there remains monophasic time frozen on the traumatic event. It can then be difficult, if not impossible, to project oneself into the future or to remember the past prior to the traumatic event. The definitions of trauma are recalled in this article and the contribution of the media to the development of trauma is, in particular, questioned. Then, from the multiphasic time model previously described, the frozen time of the trauma is reconsidered by emphasizing the interest of summoning the past and the future in the therapeutic process in order to put the temporality of the individual back in motion and continuity. More precisely, the therapy and counseling work of the therapist allow, among other things, to pass from a monophasic suspended time in which it is often necessary to welcome the individual in his/her sensoriality and corporality, to a multiphasic dynamic time in which it becomes possible for the individual to project himself/herself into the future and remember the past. The role of the group, as a containing envelope, and collective memory in the (re)construction of individual memory and self-consciousness, is also discussed. Finally, the passage from sensory fright to narrative, from traumatic sensory "cyst" to psychic elaboration, from the frozen time of trauma to the time of psychic mobilization, is developed. It is necessary to have available various therapeutic tools adapted to these different times in order to be able to reestablish a temporal, psychic and existential continuity. The effectiveness of a therapeutic approach will depend on its coherence, both for the individual and the therapist, in the context of their temporalities, resources and singularity, and of the therapeutic alliance that can develop.

[School bullying and group violence: How to occupy a place in the group by exclusion]. / Harcèlement scolaire et violence groupale : comment occuper une place dans le groupe par l'exclusion.

The prevalence of school bullying (a deliberate, repeated act of verbal, physical or relational/social aggression occurring in a situation of inequality, including cyberbullying) is high in France (10 %) as well as in other countries like the United States (more than 40 % of school children have experienced harassment at some point in their school cursus). This frequency varies by country, source of observation, school, class, and age of children. Self-questionnaires where children have to self-identify as harassing or being harassed involve a clear bias of underevaluation (even for harassed children who can feel ashamed to report explicitly harassment). The method of peer nomination of who, according to each child, has harassed or has been harassed in recent months out of all children in a class, based on mean results, is the most objective method. However, it depends on the participation rate and is not easy to implement, as some professionals consider it to be based on a denunciatory system. The fight against school bullying is a priority with regard to its possible psychological, physical and educational effects on the harassed child/adolescent, but also on the harassing child/adolescent and the spectators. In addition, the consequences of harassment are amplified in our societies by social networks with the use of SMS and Internet on mobile phones and computers. The feeling of being pursued, not only by the harassing youth but also in the eyes of the spectators is no longer limited today to the walls of the school but is also found in other environments where the harassed child/adolescent could previously recuperate from harassement (home, places of extracurricular activity, etc.). Combating school bullying requires breaking the silence and understanding its mechanisms by questioning the roles and functions of all the actors. Bullying appears to be a question of place, a place to show leadership and power but also to gain popularity for the harassing child/adolescent, a place to maintain in the group for the spectators, and a place to defend or to be established for the harassed youth. The presence of spectators, essential to the existence and maintenance of school bullying, distinguishes it from abuse; without spectators, the show cannot take place. There are indeed various actors in harassment, all of them having a major role (roles of stalker, harassed and spectator), and without which the group dynamic could not continue. It opens new perspectives of intervention based on collective responsibility but also individual responsibility, knowing that if only one spectator opposes him/herself to school bullying, harassment can stop. A part focused on each of these protagonists is presented and discussed in this article. However, there is no typology that could be reported here regarding the harassed person, the harassing one or the spectator. A model linking the various protagonists of harassment is presented and proposes that interventions take place simultaneously on these different levels, by focusing on each actor separately but also jointly in the group concerned by school bullying using discussion and role-playing. This work focuses on the ability of cognitive empathy (ability to understand the emotions of others), apparently preserved even in harassing children, and more precisely on the transition from cognitive empathy to emotional empathy (ability to experience the emotions that others feel by putting oneself in their place). If one of the fundamentals of harassment relies on an issue of place, as hypothesized, role-playing and simulation games that consist of "putting oneself in the place of the other" can be powerful mobilizers to combat harassment by allowing a change in points of view, perspectives, positions, relational modalities and behaviors. It is also important to extend interventions to larger groups representing institutions (family, school, society) with their systems of rules and laws that guarantee ethics and protect the individual within institutions. Finally, it is necessary to be aware of the possible risk of antiharassment measures, to create or reinforce an identity of harasser, harassed and/or spectator. For this reason, neither the harassed child/adolescent is designated in this article as "the victim", nor the harassing child/adolescent as "the author". The substantives (and not adjectives), the victim and the author, suggest the existence of a permanent identity persisting even outside the context of harassment and defining the individual. Similarly, the proposal of a specialized consultation in psychology and child psychiatry for harassed or harassing children/adolescents does not seem appropriate with regard to this identity issue. This underlines the importance of antibullying interventions to help build spaces for thinking where all individuals can express their feelings and experience the feelings of others, in a secure framework based on human values and clear rules, respected both at an individual and collective level, and supported by fair institutions.

Aggressive behavior: A language to be understood.

Aggressive behaviors could be considered as a dynamic of communication, in which aggression is a language to be understood, to be deciphered by two protagonists : the aggressor coping with a stressful and threatening situation and the aggressed individual coping with an aggressive acting out. The following questions are addressed: (a) What does aggression mean to the aggressor, what does it mean to the aggressed individual? (b) What does the aggressor want or try to express, and why does he or she use this mode of expression and action over another? (c) How does the aggressed individual react, and what is the impact of his or her response on the aggressor? This article reviews studies on the definition of aggression, its measurement, its developmental role and its associated risk factors in children and adolescents. First, aggression in children and adolescents with typical and atypical development is examined based on a developmental approach, clinical case studies in child and adolescent psychiatry, and an empirical study on aggression in autism. Then, in light of these studies, the problem of violence among younger and younger children and adolescents, is discussed. Finally, taking together these studies and discussion, a model is proposed that accounts for factors involved in aggressive behaviors and for different possible levels of intervention. Physical and/or psychic threats generate stress and may therefore lead to offensive or defensive aggression. Stress has to be considered in its physiological dimension (biological stress responses) and psychological dimension (perceived stress). This model reveals a vicious circle: when the main response to aggression is repression, it may reinforce physical/psychic threats and stress perceived by the aggressor, and in turn aggressive behaviors. Intervention can occur at three levels: the stressful situation, the aggressor (perception of the stressful situation and his or her response), and the aggressed individual (perception of the aggression and his or her response). This model, like all models, is limited but it offers a discussion and perspectives to understand the different links that form the "chain of aggressive behavior" and the relationships between exposure to violence and expression of violence. The article concludes on the interest of a muldisciplinary approach to aggression integrating physiological, psychological and sociological dimensions.

[Therapeutic approaches for sleep and rhythms disorders in children with ASD]. / Approches thérapeutiques des troubles du sommeil et des rythmes chez l'enfant avec TSA.

Sleep disturbances are extremely common (40-86%) in children and adolescents, especially those with autism spectrum disorders (ASD) and are often among the first symptoms identified by parents at a very early stage of their child's development. These abnormalities are among the main parental concerns when having a child with ASD and have a significant impact on the quality of life of patients, their parents, and more broadly their siblings. Sleep disorders are essentially abnormalities of the sleep-wake rhythm - primarily sleep onset insomnia or nocturnal awakenings (with difficulty falling back to sleep). These disturbances can be accompanied by other sleep disorders, requiring notably a systematic elimination of the presence of a sleep apnea or restless legs syndrome - to ensure a personalized and efficient therapeutic approach. Physiologically, the determinants of these sleep disorders are poorly understood, even though several studies point to a significant decrease in melatonin synthesis in people with ASD. Melatonin is a hormone that facilitates falling asleep and maintaining sleep and is also involved in the endogenous synchronization of internal biological clocks. However, the causal factors of this decrease in melatonin synthesis are largely unknown, involving to a small extent the genes involved in melatonin synthesis pathway. The treatment of sleep disorders is relatively systematic: after eliminating other specific sleep disorders associated with the complaint of insomnia, as well as other possible associated comorbidities (such as seizures), a global and graduated therapeutic approach must be put in place. This treatment will be non-pharmacological as a first line, then pharmacological as a second line. A number of non-pharmacological treatment strategies for sleep disorders in typically developing children and adolescents, as well as those with ASD, have been shown to be effective. This treatment requires a combination of: 1) parental education to promote sleep development; 2) setting up bedtime rituals adapted to the child's age and particularities; 3) specific behavioral strategies including bedtime fading, gradual extinction and positive reinforcement of adapted behaviors. It is very essential that the parents are accompanied throughout this therapy. Sleep hygiene and behavioral care must also take into consideration the important role of the zeitgebers of sleep-wake rhythms, i.e. the external environmental factors involved in the synchronization of the biological clocks: regular exposure to light at adapted times, regular meal and wake-up times, social activities and times for going to school. The evidence for the effectiveness of behavioral interventions in the treatment of behavioral insomnia in the typical developmental child is strong, since 94% of children show clinically significant improvements in nighttime sleepiness and waking. By contrast, only about 25% of children with ASD are improved by an approach combining sleep hygiene and behavioral therapy. Melatonin has a special and prominent place in the drug management of sleep disorders associated with ASD. Several clinical trials have shown that melatonin is effective in treating sleep disorders in patients with ASD. This work led to the European Medicines Agency (EMA) granting marketing authorization in September 2018 for a sustained-release paediatric melatonin molecule (Slenyto®). This synthetic molecule is a prolonged release melatonin (PRM) which mimics the physiological pharmacokinetic and secretory characteristics of endogenous melatonin, having a very short blood half-life and prolonged secretion for several hours during the night. A recent study evaluated the efficacy and safety of pediatric PRM (mini-tablets) in 125 children, aged 2 to 17.5 years with mainly ASD. After 15 days on placebo, the children were randomized into two parallel groups, PRM or placebo in a double-blind design for 13 weeks. At endpoint, total sleep time was increased by an average of 57.5 minutes on PRM and only 9.14 minutes on placebo (P=0.034). This difference between the two groups was already significant after three weeks of treatment (P=0.006). Sleep latency was also improved in the PRM group (-39.6 minutes) compared to placebo (-12.51 minutes) (P=0.01). Consolidated sleep duration (uninterrupted by awakenings) was improved by 77.9 minutes for the PRM group and only 25.4 minutes for the placebo group (P<0.001). PRM was well tolerated, the most frequent side effects being headache and daytime drowsiness at the same level with PRM or placebo. In addition, the acceptability by the children for swallowing the mini-tablets was excellent (100% compliance). The efficacy and tolerability of PRM was maintained over the medium and long term in the open phase, over a total study duration of 2 years.

[Children with high potential and difficulties: Contributions of clinical research]. / Les enfants à haut potentiel en difficulté : apports de la recherche clinique.

We have been sensitized to children with high intellectual potential (HIP) having difficulties given the number of children consulting in our outpatient medico-psychological centres for scholastic problems (possibly leading to school failure), anxiety disorders or behavioral disorders such as attention deficit/hyperactivity disorder (ADHD), and in which a high intellectual potential was discovered during psychological assessments. It is the contrast, and more precisely the paradox, between the high intellectual potential of these children and their scholastic difficulties (including school failure), and the psychic suffering expressed by some of them, which led us to question, challenge and propose therapeutic and educational care adapted to these children. It is in this context that we created in December 2005 the CNAHP (National Center for Assistance to High Potential children and adolescents) which is a public centre integrated into the hospital-university department of child and adolescent psychiatry at Rennes. It is noteworthy that not all children with HIP have difficulties, and children with school failure or behavioral problems are not always children with HIP. However, it is necessary not to minimize the problem raised by children with HIP with difficulties by ignoring its frequency or by considering that these children are "intelligent" enough to manage by themselves and do not need to be helped, whereas some of them can show school failure and even be de-scholarized. Indeed, based on the definition of the World Health Organization (WHO) of an intellectual Quotient (IQ) above 130 (level corresponding to a statistical threshold), the frequency of children with HIP represents 2.3% of the population of schoolchildren aged 6 to 16. The frequency is therefore not so rare. However, it remains to be determined by French epidemiological studies what is the actual frequency of children with difficulties within a population of children with HIP. The analysis of the CNAHP research data from a clinical population (children with HIP consulting for difficulties) highlights that children with HIP can show major school problems (including school failure, defined here as having or foreseeing repetition of a grade), which corresponds to 7.5% of 611 children with HIP consulting at the CNAHP) and socioemotional problems (emotional regulation disorders) in relation to their high intellectual potential. In particular, anxiety disorders were the most frequent psychiatric disorders observed in this population (40.5%) and were significantly associated with high verbal potential. This significant association requires further studies to avoid establishing a simplistic unidirectional and reductive linear cause-effect relationships. Indeed, a high verbal potential can elicit and/or reinforce anxiety-producing representations, but anxiety disorders may also lead to a defensive over investment of verbal language. The results are discussed in this article and suggest that scholastic and/or psychological difficulties encountered by some children with HIP can be related to their high intellectual potential. It is necessary to develop therapeutic and educational care adapted to these children from a better understanding, based on research results, of their possible difficulties but also cognitive abilities. Even when children with HIP have scholastic and/or psychological difficulties, some of their cognitive skills can be preserved contrary to appearances, with for example, as seen in the CNAHP results, excellent attentional capacities shown by cognitive tests contrasting with behavioral attention deficit reported by parents. These skills are important to identify as they are resources which support the therapeutic and educational project. It is probably through an articulation among professionals from national education, health and research, in alliance with the family (parents, child, and siblings), that advances will be made. In the same way that professionals have been interested in children with intellectual disabilities, it is important to be concerned by children with HIP and difficulties located at the other end of the continuum. It is a question of ethics which concerns both caregivers and teachers. It is also a societal issue that concerns all of us given that the expression of high intellectual and creative potential in children may be essential to the societal development of innovative strategies and each nation's future. Finally, the discussion can be extended to all children, independent of their potential. What we learn from children with HIP and difficulties can be applied to each child: it is important at family, school and societal levels to facilitate the expression of the potential of children, to value their skills, and to help them to remove possible inhibitions of their potential based on individualized projects. The acceptance of singularity and differences in children can contribute to tolerance and the development of creativity, in the interest of the subject and of society.

Time perception of simultaneous and sequential events in early-onset schizophrenia.

Timing disorders in schizophrenia are a well-known phenomenon. However, no studies have yet assessed the role of temporal distortions in early-onset schizophrenia (EOS), despite evidence that distorted time perception may share genetic risk factors with schizophrenia and may be a useful indicator in identifying individuals at risk for schizophrenia. In the present study, we investigated the ability of 10 patients with EOS (mean age = 21.5 years, SD = 6) matched with 20 healthy control participants (mean age = 25.3 years, SD = 4.6) in order to compare the durations of two visual events, presented either sequentially or overlapping in time, along with neuropsychological assessments of attention, working memory, and executive functions. Each participant had to judge a total of 336 stimuli. We found that temporal overlap had a greater negative effect on ability to judge the duration of a pair of stimuli in EOS patients than in healthy control participants. In addition, EOS patients showed impairments in attention and executive functions. Furthermore, in EOS patients, the scores for executive and attentional functions were significantly correlated with accuracy of temporal estimation in the overlap condition (r = 0.31, p < 0.05 and r = 0.57, p < 0.05, respectively). These preliminary results suggest that impairments in neuropsychological functions participate in the deficit in time estimation observed in patients with EOS. These conclusions highlight the importance of testing time perception in patients with EOS and could contribute to the development of cognitive remediation-based therapy for these patients.

[Time perceptions and representations]. / Représentations et perceptions du temps.

Representations of time and time measurements depend on subjective constructs that vary according to changes in our concepts, beliefs, societal needs and technical advances. Similarly, the past, the future and the present are subjective representations that depend on each individual's psychic time and biological time. Therefore, there is no single, one-size-fits-all time for everyone, but rather a different, subjective time for each individual. We need to acknowledge the existence of different inter-individual times but also intra-individual times, to which different functions and different rhythms are attached, depending on the system of reference. However, the construction of these time perceptions and representations is influenced by objective factors (physiological, physical and cognitive) related to neuroscience which will be presented and discussed in this article. Thus, studying representation and perception of time lies at the crossroads between neuroscience, human sciences and philosophy. Furthermore, it is possible to identify several constants among the many and various representations of time and their corresponding measures, regardless of the system of time reference. These include the notion of movements repeated in a stable rhythmic pattern involving the recurrence of the same interval of time, which enables us to define units of time of equal and invariable duration. This rhythmicity is also found at a physiological level and contributes through circadian rhythms, in particular the melatonin rhythm, to the existence of a biological time. Alterations of temporality in mental disorders will be also discussed in this article illustrated by certain developmental disorders such as autism spectrum disorders. In particular, the hypothesis will be developed that children with autism would need to create discontinuity out of continuity through stereotyped behaviors and/or interests. This discontinuity repeated at regular intervals could have been fundamentally lacking in their physiological development due to possibly altered circadian rhythms, including arhythmy and asynchrony. Time measurement, based on the repetition of discontinuity at regular intervals, involves also a spatial representation. It is our own trajectory through space-time, and thus our own motion, including the physiological process of aging, that affords us a representation of the passing of time, just as the countryside seems to be moving past us when we travel in a vehicle. Chinese and Indian societies actually have circular representations of time, and linear representations of time and its trajectory through space-time are currently a feature of Western societies. Circular time is collective time, and its metaphysical representations go beyond the life of a single individual, referring to the cyclical, or at least nonlinear, nature of time. Linear time is individual time, in that it refers to the scale of a person's lifetime, and it is physically represented by an arrow flying ineluctably from the past to the future. An intermediate concept can be proposed that acknowledges the existence of linear time involving various arrows of time corresponding to different lifespans (human, animal, plant, planet lifespans, etc.). In fact, the very notion of time would depend on the trajectory of each arrow of time, like shooting stars in the sky with different trajectory lengths which would define different time scales. The time scale of these various lifespans are very different (for example, a few decades for humans and a few days or hours for insects). It would not make sense to try to understand the passage of time experienced by an insect which may live only a few hours based on a human time scale. One hour in an insect's life cannot be compared to one experienced by a human. Yet again, it appears that there is a coexistence of different clocks based here on different lifespans. Finally, the evolution of our society focused on the present moment and choosing the cesium atom as the international reference unit of time measurement (cesium has a transition frequency of 9.192.631.77000 oscillations per second), will be questioned. We can consider that focusing on the present moment, in particular on instantaneity rather than infinity, prevents us from facing our own finitude. In conclusion, the question is raised that the current representation of time might be a means of managing our fear of death, giving us the illusion of controlling the uncontrollable, in particular the passage of time, and a means of avoiding to represent what many regard as non-representable, namely our own demise.

[Time perception and schizophrenia: Phenomenological and neuropsychological approach]. / Perception temporelle et schizophrénie : approche phénoménologique et neuropsychologique.

OBJECTIVES: Based on clinical, phenomenological and neurobiological observations, psychiatrists often report a deficit in time estimation in patients with schizophrenia. Cognitive models of time estimation in healthy subjects have been proposed and developed for approximately 30 years. The investigation of time perception is pertinent to the understanding of neurobiological and cognitive abnormalities in schizophrenia. Brain lesions and neuroimaging studies have shown that the critical brain structures engaged in time perception include the prefrontal and parietal lobes, thalamus, basal ganglia and cerebellum. These brain areas have been implicated in the physiopathology of schizophrenia in that there is impaired coordination of activity among these regions. Clinical and experimental date strongly suggest that patients with schizophrenia are less accurate in their ability to estimate time than healthy subjects. The specificity of these clinical and behavioral impairments is still in question. The aims of this article are to present an overview of the literature regarding time estimation and schizophrenia, to discuss specific issues related to how perceptual dysfunction in schizophrenia may lead to abnormalities in time perception, and to propose new perspectives towards an integrative approach between phenomenology and neuroscience. METHODS: We present a review of the literature describing the current theory in the field of time perception, which is supported by a connectionist model, postulating that temporal judgment is based upon a pacemaker-counter device that depends mostly upon memory and attentional resources. The pacemaker emits pulses that are accumulated in a counter, and the number of pulses determines the perceived length of an interval. Patients with schizophrenia are known to display attentional and memory dysfunctions. Moreover, dopamine regulation mechanisms are involved in both the temporal perception and schizophrenia. DISCUSSION: It is still unclear if temporal impairments in schizophrenia are related to a specific disturbance in central temporal processes or are due to certain cognitive problems, such as attentional and memory dysfunctions, or biological abnormalities. While psychopathological and phenomenological work strongly suggests that time perception disturbance may be the key or core symptom in schizophrenia, neuroscience studies have failed to do the same. The question of specificity of temporal perception impairments in schizophrenia remains contested. Neuroscience studies suggest that time symptoms in patients with schizophrenia are only secondary to thought disorders and primary cognitive impairments. This debate refers to the etiologic/organic versus psychogenesis/psychological dichotomy and may be over-taken. CONCLUSION: Clinical evidence associated with psychopathological, biological and cognitive theories strongly suggests that patients with schizophrenia have a deficit in time perception. Discrimination and reproduction of durations have been found to be constantly impaired and disorganized. There is still much work to be done to identify the exact sources of variability in temporal judgments in schizophrenia, and the study of developmental course of time perception could be an interesting route. Regardless of the role of temporal deficits in the pathogenesis of schizophrenia (as a general cognitive disorder or a core role), clinical and phenomenological data encourage us to conduct further studies, especially in the field of developmental psychology.

Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia.

Three common missense variants of the Disrupted in Schizophrenia 1 (DISC1) gene, rs3738401 (Q264R), rs6675281 (L607F) and rs821616 (S704C), have been variably associated with the risk of schizophrenia. In a case-control study, we examine whether these gene variants are associated with schizophrenia and ultra-resistant schizophrenia (URS) in a population of French Caucasian patients. The URS phenotype is characterized according to stringent criteria as patients who experience no clinical, social and/or occupational remission in spite of treatment with clozapine and at least two periods of treatment with distinct conventional or atypical antipsychotic drugs. We find a significant association between DISC1 missense variants and URS. The association with rs3738401 remains significant after appropriate correction for multiple testing. These results suggest that the DISC1 rs3738401 missense variant is statistically linked with ultra-resistance to antipsychotic treatment.

Reframing schizophrenia and autism as bodily self-consciousness disorders leading to a deficit of theory of mind and empathy with social communication impairments.

Prior observations and studies suggest self-consciousness disorders in schizophrenia and Autism Spectrum Disorder (ASD), two neurodevelopmental disorders sharing social communication impairments. First, the relationships between schizophrenia and autism are explored regarding social communication impairments. Then, self-consciousness disorders in schizophrenia and autism are described and discussed in relation with impairments of body self leading to impairments of self-other differentiation, a deficit of theory of mind and empathy, and their consequences on social communication. Also, neurological dysfunction involved possibly in self-consciousness disorders in schizophrenia and autism is presented. In conclusion, a new model is proposed integrating results of studies presented here and stating the existence of bodily self-consciousness disorders in schizophrenia and autism associated with altered/absent intermodal sensory integration (especially visual-kinesthetic-tactile integration). This would result in problems of self-other differentiation, leading in turn to a deficit of theory of mind and empathy as well as social communication impairments. This model opens new perspectives to understand better self-consciousness disorders and social communication impairments in schizophrenia and ASD and to develop therapeutic strategies.

Repint of "Reframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity".

Clinical and molecular genetics have advanced current knowledge on genetic disorders associated with autism. A review of diverse genetic disorders associated with autism is presented and for the first time discussed extensively with regard to possible common underlying mechanisms leading to a similar cognitive-behavioral phenotype of autism. The possible role of interactions between genetic and environmental factors, including epigenetic mechanisms, is in particular examined. Finally, the pertinence of distinguishing non-syndromic autism (isolated autism) from syndromic autism (autism associated with genetic disorders) will be reconsidered. Given the high genetic and etiological heterogeneity of autism, autism can be viewed as a behavioral syndrome related to known genetic disorders (syndromic autism) or currently unknown disorders (apparent non-syndromic autism), rather than a specific categorical mental disorder. It highlights the need to study autism phenotype and developmental trajectory through a multidimensional, non-categorical approach with multivariate analyses within autism spectrum disorder but also across mental disorders, and to conduct systematically clinical genetic examination searching for genetic disorders in all individuals (children but also adults) with autism.

Reframing autism as a behavioral syndrome and not a specific mental disorder: Implications of genetic and phenotypic heterogeneity.

Clinical and molecular genetics have advanced current knowledge on genetic disorders associated with autism. A review of diverse genetic disorders associated with autism is presented and for the first time discussed extensively with regard to possible common underlying mechanisms leading to a similar cognitive-behavioral phenotype of autism. The possible role of interactions between genetic and environmental factors, including epigenetic mechanisms, is in particular examined. Finally, the pertinence of distinguishing non-syndromic autism (isolated autism) from syndromic autism (autism associated with genetic disorders) will be reconsidered. Given the high genetic and etiological heterogeneity of autism, autism can be viewed as a behavioral syndrome related to known genetic disorders (syndromic autism) or currently unknown disorders (apparent non-syndromic autism), rather than a specific categorical mental disorder. It highlights the need to study autism phenotype and developmental trajectory through a multidimensional, non-categorical approach with multivariate analyses within autism spectrum disorder but also across mental disorders, and to conduct systematically clinical genetic examination searching for genetic disorders in all individuals (children but also adults) with autism.

[From a categorical diagnostic approach to a dimensional approach for mental disorders: interest of sex differences]. / D'une approche nosographique catégorielle à une approche dimensionnelle des troubles mentaux: intérêt de la différenciation sexuelle.

A strong prevalence of females or males is often found in mental disorders. Based on examples of anorexia (90% females) and autistic disorder (80 to 90% males), arguments that allow a better understanding of these different sex ratios are presented. The role of certain sociocultural factors in the onset of anorexia is developed. The predominance of males in autistic disorder has led to genetic and hormone-based biological hypotheses. However, it is also possible that the cultural representation of sex roles and its effects (expectation, different attitudes and behaviors depending on the child's gender) influence the development of social interaction and communication domains which are impaired in autistic disorder. Indeed, according to most studies, parents solicit and stimulate more social interaction and communication (eye contact specially during the first months of life, vocalizations then verbal language, emotional expression) in girls than in boys during the first three years of life, which corresponds to the period when autistic disorder appears. It is possible that because girls are more solicited than boys in social interaction and communication domains, during a sensitive (or critical) period of development, we may observe that girls show less autistic impairment in reciprocal social interaction and verbal or non-verbal communication, which are two of the three main domains of autistic disorder. It is also possible that impairments in social interaction and communication may be identified earlier for girls than for boys, which could lead to earlier therapeutic care for girls. Indeed, if parents have greater expectations for girls in social interaction and/or communication domains, they may worry more for their girl than for their boy with regard to developmental delay in these domains, and then may ask for professional advice earlier. This is what we have observed in our clinical practice and research, in which we conducted a follow-up in young girls showing autistic disorder aged two and half years old and who evolved positively; in contrast we have observed that parents bring their son for professional advice later, after kindergarten begins. Finally, a more complex, non-linear model is proposed in which biological genetic factors (such as sex-linked chromosomes) and/or hormonal factors (such as sex hormones) may play a role in differentiation of girls' and boys' behavior from birth. These different behaviors would induce differentiated expectations and attitudes in parents depending on the child's gender, which in turn would reinforce sex-related characteristic behaviors in the child. Thus, there may be a continuum in different behavioral domains (for example, boys would interact and communicate less than girls, and girls would express more their emotions), with mental disorders occurring at the extremes of this continuum (for example, autistic disorder for certain boys and anxiety disorder for certain girls). This hypothesis fits within an integrated psycho-biological approach that takes into account sex differences in mental disorders; it stems from a model in which a dimensional conception of mental disorders replaces a categorical nosographical one. New perspectives could be envisioned concerning the identification, follow-up and treatment of mental disorders (or sub-types of mental disorders), which are currently considered to belong to different nosographical categories, but which could overlap through shared common dimensions.

[Gifted children in difficulty: from attention deficit hyperactivity disorder to depression and school failure]. / Enfants surdoués en difficulté: de l'hyperactivité avec déficit attentionnel a la dépression et l'echec scolaire.

We became interested in gifted children with difficulties based on the number of children who were addressed to our outpatient units for behavioral problems such as Attention Deficit Hyperactivity Disorder, scholastic problems or symptoms of depression, and for whom we identified a high intellectual potential. This article treats in particular Attention Deficit Hyperactivity Disorder (ADHD) which is observed for certain gifted children and can cover a depression and lead to school failure. How can ADHD in gifted children be interpreted? Based on our clinical experience and the literature, we propose that this disorder stem from need for external and internal stimulation. Several hypotheses concerning this idea will be then discussed, notably concerning their therapeutic implications.

Genetic architecture of testis and seminal vesicle weights in mice.

Comparisons across 13 inbred strains of laboratory mice for reproductive organ (paired seminal vesicles and paired testes) weights indicated a very marked contrast between the C57BL/6By and NZB/BINJ mice. Subsequently these strains were selected to perform a quantitative genetic analysis and full genome scan for seminal vesicle and testis weights. An F(2) population was generated. The quantitative genetic analyses indicated that each was linked to several genes. Sixty-six short sequences for length polymorphism were used as markers in the wide genome scan strategy. For weight of paired testes, heritability was 82.3% of the total variance and five QTL contributed to 72.8% of the total variance. Three reached a highly significant threshold (>4.5) and were mapped on chromosome X (LOD score 9.11), chromosome 4 (LOD score 5.96), chromosome 10 (LOD score 5.81); two QTL were suggested: chromosome 13 (LOD score 3.10) and chromosome 18 (LOD score 2.80). Heritability for weight of seminal vesicles was 50.7%. One QTL was mapped on chromosome 4 (LOD score 9.21) and contributed to 24.2% of the total variance. The distance of this QTL to the centromere encompassed the distance of the QTL linked with testicular weight on chromosome 4, suggesting common genetic mechanisms as expected from correlations in the F(2). Both testis and seminal vesicle weights were associated with a reduction in the NZB/BINJ when this strain carried the Y(NPAR) from CBA/H whereas the Y(NPAR) from NZB/BINJ in the CBA/H strain did not modify reproductive organ weights, indicating that the Y(NPAR) interacts with the non-Y(NPAR) genes. The effects generated by this chromosomal region were significant but small in size.

Neuronal and behavioral differences between Mus musculus domesticus (C57BL/6JBy) and Mus musculus castaneus (CAST/Ei).

Previous studies have demonstrated that classical inbred strains of laboratory mice do not exhibit large genetic distances when simple sequence repeats (SSRs) are used to test for their polymorphisms whereas mice from wild origin exhibit high polymorphisms (more than 90%) for these sequence when compared with classical inbred strains of laboratory mice. The difference between Mus musculus castaneus and C57BL/6J reaches 98% and F1s male and female are fertile. These two properties pave the way for gene mapping derivating segregating generations between these strains. The phenotypical characteristics of Mus musculus castaneus have not been investigated, unfortunately. The first screening of Mus musculus castaneus and C57BL/6By was carried out for sensorial and motor development, spontaneous behavior in new environment, paw preference, maternal behavior, aggression in two different situations and time to learn escape in a water maze. Morphometry of hippocampus and weight of the male reproductive organs for measures that have been reported to be correlated with several of the examined behavior are also reported. The authors tested also reactivity to one drug (beta-CCM) revealing seizure proneness. The two strains differ for 69% of the reported measures. Comparison to other strains for the same measures obtained in the laboratory for identical tests with mice reared in identical situations provided the mean to compare Mus musculus castaneus with a large set of more or less traditional mice. This strain has the most extreme position for 80% of the comparisons.

Linkage between brain serotonin concentration and the sex-specific part of the Y-chromosome in mice.

The implication of the sex-specific part of the Y-chromosome (YS-SP) on brain serotonin (5-HT) level was investigated using congenic strains for this chromosomal region. The 5-HT level, which was higher in the NZB than in the CBA/H strain of mice, was depleted by the transfer of the YS-SP from NZB on CBA/H whereas the transfer of the YS-SP from CBA/H on NZB had no effect. The variations of 5-HT levels were not correlated with plasma testosterone concentration which is also dependent of the YS-SP.

Plasma androgens in autism.

Plasma levels of testosterone and the adrenal androgen dehydroepiandrosterone sulfate (DHEA-S) were measured in male autistic subjects (31 prepubertal, 8 postpubertal), mentally retarded/cognitively impaired subjects (MR, 12 prepubertal), and normal control subjects (NC, 10 prepubertal, 11 postpubertal). Mean levels of plasma testosterone were similar in the postpubertal autistic (4.54 +/- 1.12 ng/ml) and postpubertal NC (5.02 +/- 1.87 ng/ml) groups. Plasma DHEA-S levels in postpubertal autistic (2170 +/- 1020 ng/ml) and postpubertal NC (1850 +/- 777 ng/ml) groups also were not significantly different. Similarly, no significant group differences were seen for testosterone or DHEA-S in the prepubertal autistic, MR, or NC individuals, although prepubertal MR individuals with cerebral palsy did have increased plasma DHEA-S levels compared to age-matched MR or NC individuals. Significant negative correlations were found between testosterone and whole blood serotonin (5-HT) levels in the combined (all subjects, all ages) groups and in the autistic group, suggesting that the effect of puberty on whole blood 5-HT may deserve further study. Data indicate that altered secretion of the androgens is not a common feature of autism. However, abnormalities of adrenal androgen secretion may be present in individuals with cerebral palsy.

[Study of the relationships between self-injurious behavior and pain reactivity in infantile autism]. / Etude des conduites auto-agressives, de la réactivité à la douleur et de leurs interrelations chez les enfants autistes.

Autism can be considered as an early general developmental disorder, characterized by problems of social interaction, problems of verbal and non verbal communication, and behavioral or ideational stereotypes. However, within autism we observe a clinical heterogeneity of autistic disorders which suggests the possibility of autistic subtypes. Several authors hypothesize an analgesia among autistic children; this analgesia may be related to self-mutilation found among autistics. The current research had two objectives: 1) to develop and validate evaluation tools for measuring aggression directed towards the self (Yale-Paris Self-Injurious Behavior Scale: YAPA SIB) and pain reactivity (Pre-Linguistic Behavioral Pain Reactivity Scale: PLBPRS); instruments appropriate for autistics and capable of showing different behavioral sub-types; 2) to study in 80 autistic children pain reactivity, self-injurious behavior, and their relation in different observational situations. The results show that the scales of self-injurious behavior and pain reactivity have good discriminative capacity, good test-retest reliability, and good validity. The results suggest additionally that the apparent decreased pain reactivity observed in autistics does not derive from a real analgesia but from a different mode of pain expression related to difficulties with verbal communication, body representation and certain cognitive disorders (learning disorders, problems representing sensations and emotions, problems establishing cause-effect relationships). Additionally, there is a significant relationship between certain self-injurious behaviors and the apparent reduced pain reactivity. Interpretations of this result are presented and the possible role of stress in autism is discussed.

A comparative study of defense styles of bulimic, anorexic and normal females.

We have compared the defense styles of anorexic (N = 41), bulimic (N = 37) and normal females (N = 72) living in Paris, using the Bond Defense Style Questionnaire relating to 17 defenses: sublimation, anticipation, suppression, undoing, idealization, reaction formation, projection, passive aggression, acting out, isolation, devaluation, autistic fantasy, denial, displacement, dissociation, splitting and somatization. The objective of this study was to better understand the personality structure in terms of psychological defenses of adolescent girls and young women suffering from anorexia or bulimia nervosa (DSM-III-R). Data showed significant differences of psychological functioning between control subjects and eating disorder subjects, particularly for the projection, undoing and sublimation defenses. Anorexics differed from the bulimic females only on the passive aggression, isolation and devaluation defenses. These data are discussed in relation to the hypothesis that anorexics and bulimics can be situated on the same continuum ranging from normal to eating disorders with certain common psychological features as risk factors shared by the eating disorder females.