[ADHD during childhood and subsequent psychotic disorder: A link?] / TDAH dans l'enfance et trouble psychotique à l'âge adulte : quel lien ?

OBJECTIVES: Attention Deficit with/without Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with frequent comorbid psychiatric disorders. Several studies have underlined the increased risk of developing a psychotic disorder subsequent to a childhood ADHD. The aim of our review is not only to clarify this association and the related physiopathology but also to understand the consequences for therapeutic management. METHODS: We processed a narrative review of available literature based on a research of the PubMed database. Articles related to ADHD and psychotic disorder on a genetical, clinical or biological level were selected by one of the authors. RESULTS: ADHD and psychotic disorders share neonatal, environmental, and genetic risk factors. On a neurobiological level, both disorders are concerned by a dysfunction of the dopaminergic system with an abnormal regulation of dopaminergic neurons' phasic and tonic activity. Our review aims to explain the « dynamic ¼ model of dopaminergic dysfunctions and propose some guidance for pharmacological treatment of ADHD, with or without psychotic disorder. This model offers a better understanding of why methylphenidate is not associated to an increased risk of psychotic disorder and could act as a protective factor. Association between ADHD and psychotic disorders could be explained by some comorbidities such as substance use disorders which are frequently associated with both conditions and could act as mediator in the genesis of psychotic disorders following ADHD during childhood. Our review also focuses on an epidemiological bias that could be found in some studies such as possible diagnostic errors, as some non-specific clinical signs could be found in both late diagnosed ADHD and in "at risk mental state" of psychosis. CONCLUSION: ADHD and psychotic disorders share common risk factors, neurobiological pathways and clinical symptoms. Perspectives for future studies are proposed considering a dimensional aspect of psychiatric disorders using, for example, Research Domain Criteria and exploring the link between the two conditions.

[All you need to know about methylphenidate (and dared not ask)]. / Tout ce que vous devez connaître sur le méthylphénidate (sans oser le demander ).

Methylphenidate (MPH) remains the only accessible psychostimulant used in France in the attention and behavior disturbances of attention deficit disorder with or without hyperactivity (ADHD). Its prescription has been extended during the past decade to other neurodevelopmental disorders in children and adolescents, also associated with a deficit of attentional resources or, more broadly, fragility of executive functions. Despite its efficiency, validated by more than 400 randomized controlled and double-blind studies, and the good tolerance of MPH in these indications, this treatment remains limited in France because of many fears and other prejudices on the part of medical practitioners and/or families. This article, resulting from the complementary viewpoints of a psychiatrist and a neuropharmacologist, is not intended to advocate MPH but to present, in a concise and nuanced manner, the approved scientific data justifying and framing this prescription.

[The schizophrenic's chilhood]. / Enfance du schizophrène.

Pathology of adolescence and young adult, schizophrenia can begin in very rare cases during childhood. Two early clinical forms of the disorder have been identified by epidemiological studies: one beginning at the age of 15; the other around 9 years old; While many questions remain unsanswered about the neurobiological and environmental factors - common or distinct - of these two clinical phenotype, both are related to a profoun and lasting alteration of the neurocognitive development whose origin would clearly go back to infancy or to the antenal period. Here we will present a possible story back of schizophrenia in the light of the latest neuroscientific studies in imagery and genetics from adolescence to antenal period.

[Very early onset schizophrenia]. / Schizophrénie à début très précoce.

Very early onset schizophrenia begins before the age of 13. This form of schizophrenia is particularly difficult to diagnose. The differential diagnosis is difficult because some psychotic signs can be passing or be representative of an anxious or depressive disorder. The differential diagnosis with the autistic spectrum disorder is also complex. Finally, other disorders are associated in the majority of the cases. It is a neurodevelopmental disorder with premature cerebral anomalies engendered by the interaction of genetic factors and environmental factors. There seems be a real continuity between the very early form and the adult form although very early onset schizophrenia is a severe form of the disorder which carries a relatively poor prognosis. Its outcome depends both on early screening, the quality of diagnosis and on the speed of multidisciplinary interventions offered.

[The Severe Chronic Irritability Concept: A clinical dimension to consider in child and adolescent]. / Le concept d'irritabilité chronique sévère : une dimension clinique à prendre en compte chez l'enfant et l'adolescent.

INTRODUCTION: For a decade, the concept of irritability has known a renewed interest in infant and child psychopathology. Indeed, longitudinal follow-up studies clearly highlighted their predictive value - in the short, medium and long terms - of a broad field of behavioral disorders and emotion dysregulation. This dimensional and transnosographic approach of irritability, coupled with the latest neuroscience data, points out that irritability could be the equivalent of a psychopathological marker, covering both a neurobiological, cognitive and emotional component. It is a major challenge today to better understand the developmental sequence of severe chronic irritability and its predictive influence on the etiology of mental disorders from childhood to adulthood. METHOD: We briefly review here the latest current data on this topic. RESULTS: The important point is that chronic and non-episodic irritability in children, associated with strong emotional sensitivity to negative events and frequent access of anger, could have a predictive value for progression to anxiety disorder or severe mood disorder but not to bipolar disorder as it was believed until now. The risk of developing a bipolar disorder would be more frequently correlated with the notion of transient and episodic irritability in a context of previous family history of bipolar disorder. CONCLUSION: Further studies are expected to narrow the discriminative validity of this notion of severe irritability and confirm or not its relevance as a major clinical criterion of Severe Mood Disorders in children and adolescents introduced in the last version of DSM (DSM-5).

[Developmental approach of executive functions: From infancy to adolescence]. / Approche développementale des fonctions exécutives : du bébé à l'adolescence.

Given the importance of the relationship between executive function (EF) and many aspects of child development - including the development of reasoning, emotion regulation, school performance, and wider self-regulation itself - research on the development of EF from infancy to the end of adolescence has become one of the scientific priorities of the last decade. Improving our knowledge on the maturative trajectory of EF and the functional weight of different internal and environmental factors, supposed to optimize their efficiency, can only promote a better understanding of EF and its role in the normal development of the child as well as of those at risk of poor outcome either because of neurodevelopmental disorders or psychopathological disorders. This article aims to update the recent literature in this area. It appears that executive function grows very gradually and evolves from a relatively simple and unitary model in young children to a more complex one - differentiated, integrated, and tripartite - in adolescence.

[Learning disorders in ADHD: How are they related?] / Troubles d'apprentissage dans le trouble de déficit de l'attention avec ou sans hyperactivité : quelle est la nature du lien ?

Learning difficulties in general and learning disabilities in particular are almost constant in attention deficit disorder with or without hyperactivity (ADHD). Despite a major research effort, the extent and diversity of these comorbid events still raise many questions about the exact nature of their pathogenetic condition (simple consequences of ADHD or specific related disorders?) and consequently the best way to support them. This article aims to present a brief review of the current data.

[From tic disorders to Tourette syndrome: current data, comorbidities, and therapeutic approach in children]. / Des tics moteurs au syndrome de Gilles de la Tourette : données actuelles, comorbidités et principes de prise en charge thérapeutique chez l'enfant et l'adolescent.

Motor tics are frequently observed in children during development. Usually transient and benign, they can become chronic over time, join various morbid disorders (vocal tics, attention deficit and hyperactivity disorder, and obsessive-compulsive disorders) and move toward genuine Tourette syndrome. In this case, it will be necessary to prevent impacts - mainly in terms of quality of life and emotional and relational problems - using a global therapeutic strategy combining psychoeducational approaches with appropriate medication.

[Suicide attempts of 48 children aged 6-12 years]. / Tentatives de suicide chez 48 enfants âgés de 6 à 12ans.

AIM: Research is limited on suicide attempts in children under 13 years of age. The objective of this study was to provide an in-depth description of this population. MATERIALS AND METHODS: The present study is both retrospective and descriptive. Data were collected retrospectively from a file containing the causes for hospitalization of each child admitted into the Department of Child Psychiatry at the hôpital Femme-Mère-Enfant (hospices civils de Lyon). We included all patients under 13 years of age who were hospitalized for a suicide attempt between 2008 and 2011. The methods used to collect the medical records consisted in using a form made up of four major parts: suicide attempts, social environment, medical history, and therapy. RESULTS: The 26 girls and 22 boys included had a mean age of 11.52 years. The boys were younger than the girls (P=0.047) and their parents were usually separated (P=0.034). The boys used more violent means to commit suicide in comparison to the girls (P=0.048). On average, children using violent means were younger (P=0.013). Boys underwent more psychotherapy (P=0.027) and were prescribed more psychotropic medication in comparison to girls (P=0.051). Adjustment disorders (37.5%) and depression (27%) were the two main diagnoses for hospitalization. They were hospitalized on average (±standard deviation) 9.6 days (±10 days). Psychotherapy was organized when leaving the hospital (98%) with legal measures (8.3%), change of residence (12.5%), and prescription of psychotropic drugs (37.5%). None had physical complications. DISCUSSION: In children under 13 years of age, attempted suicide was more frequent in girls than boys. However, the sample included 18 girls and nine boys who were 12 years old (sex ratio of 12-year-olds, 0.5). There were more boys (16 boys/eight girls) in the children under 12 (sex ratio of 8- to 11-year-olds, 1.6). Children under 11 used more violent means (P=0.01). The literature also reports that more violent means lead to a greater risk of death by suicide. Consequently, suicidal behavior in children under 11 years of age is closer to a behavior of a person who has committed suicide than an adolescent attempting suicide. As a result of the sex ratio and non-violent means, 12-year-old children's behavior can be considered like that of adolescents. One factor that could explain children's attempted suicide is family cohesion. The children in this study were most often from broken families and had a difficult relationship with their parents. From 1981 to 1985, more than 50% of children who consulted for their first suicide attempt were not hospitalized. Now hospitalization is recommended for all children who consult for attempted suicide. They are hospitalized on average 8.9-9 days. Individual psychotherapy is systematic. The main difference between the treatments for adolescents and children is the importance of the social worker who will require legal measures or changing residences when necessary. CONCLUSION: The sex ratio in 6- to 12-year-olds attempting suicide is higher than the sex ratio in adolescents attempting suicides. Insecure attachment was found in all families in this sample. This population is particularly at risk knowing that in adulthood, the risk of death by suicide is higher when there is a background of attempted suicide by violent methods. These children should always be hospitalized for a psychological and socioenvironmental evaluation.

[Childhood onset schizophrenia: current data and therapeutic approach]. / La schizophrénie infantile : données actuelles et principes de prise en charge thérapeutique.

Childhood schizophrenia is a rare but serious developmental disorder affecting most of the fields involved in the child's adaptive functioning: motor, emotional, cognitive, and social. The clinical expression of the disorder mainly depends on the child's age and the IQ level at the time the first clinical symptoms appear. The progression of childhood schizophrenia is generally poor, with different outcome studies suggesting a continuity of the process between childhood and adulthood. This stresses the importance of diagnosing the disorder early and initiating the adapted therapeutic measures as quickly as possible, including cognitive remediation (a new therapeutic tool to correct or anticipate cognitive disorders), which can prevent pejorative development.

[A cross-sectional study of trait-anxiety in a group of 111 intellectually gifted children]. / Étude transversale de l'anxiété trait dans un groupe de 111 enfants intellectuellement surdoués.

INTRODUCTION: Intellectually gifted children are often thought to display a high risk for psychopathology. However, this assertion has received only few direct arguments to date, and there is in fact a lack of knowledge on this subject. The aim of this study was to compare trait-anxiety - which is considered as a sensitive and early indicator of psychoaffective difficulties in children - in intellectually gifted children to the norm. METHODS: One hundred and eleven children aged 8 to 12 and with an intellectual quotient (IQ) higher than 129 participated in the study. They were recruited in a hospital department of child and adolescent psychiatry and through psychologists' private practice, where they attended consultation because of academic underachievement and/or social maladjustment. All the children were examined by trained psychiatrists and psychologists: none had a present or past medical or psychiatric condition and, additionally, none had an elevated score on the French version of the Children's Depressive Rating Scale Revised (Moor & Mack, 1982). Parents filled in a questionnaire for the collection of socio-demographic data and children answered the French version of the Revised-Children's Manifest Anxiety Scale (R-CMAS; Reynolds, 1999), a 37-items self-assessment of trait-anxiety, the psychometric properties of which have been validated in children with high IQ. DATA ANALYSIS: Mean scores and subscores on the R-CMAS in the whole studied group and as a function of gender and age were compared to French normative data (Reynolds, 1999) by calculation of 95% confidence intervals; subgroups were compared using Student's t-tests. Proportions of children who's score and subscores exceeded anxiety cut-off norms were compared to normative data using chi-square tests. Statistical significance was considered at the P<0.05 level. RESULTS: The studied group comprised mainly boys, and members of a sibling. Parents mainly lived as man and wife, had high academic levels, and had a professional activity. The confidence intervals of the R-CMAS scores and subscores all comprised their normative value, which denotes that no difference was statistically significant. Comparisons for age and gender showed no significant difference. Proportions of results exceeding the cut-off scores and subscores did not significantly differ from the norms. DISCUSSION: General and dimensional trait-anxiety levels in the studied group were comparable to normative data. These results are in accordance with previous studies of trait-anxiety in children and adolescents with high IQ, which all showed normal or decreased levels. These findings do not corroborate the hypothesis that intellectual giftedness constitutes a risk factor for psychopathology. LIMITS: The studied group was a clinical one, which could limit the generalisation of the results. However, mental disorders were ruled out, and the psychometric and socio-demographic characteristics of the group were in keeping with those described for the general population of gifted children. Moreover, considering that participant children displayed academic underachievement and/or social maladjustment, it can be supposed that their anxiety levels were not lower than those in the general population of gifted children. Secondly, the potentially confusing effect of socio-demographic variables (underrepresentation of low socio-economic levels and single-parent families) could not be statistically taken into account, due to the absence of a specific control group. CONCLUSION: Intellectually gifted children seem not to display increased trait-anxiety. However, further studies are necessary to investigate psychological functioning in gifted children and their risk for psychopathology.

[Combination of external irradiation and androgen suppression for prostate cancer: facts and questions]. / Radiothérapie et hormonothérapie pour le cancer de la prostate: acquis et interrogations.

The combination of radiotherapy and androgen suppression with luteinizing hormone releasing hormone agonist is mainly devoted to locally advanced prostate cancer and intermediate or poor risk localized prostate cancer. They are based on phase III randomized trials which have shown that for locally advanced prostate cancer, a four-month complete androgen blockade initiated two months prior radiotherapy and stopped at the completion of radiotherapy increased overall survival in patients with Gleason scores 2-6, meanwhile, an adjuvant long-term androgen suppression (2.5 to three years) improved significantly the overall survival. Complete androgen blockade with a four to six months duration, combined with external irradiation, enhanced the overall survival in patients with intermediate or poor risk localized prostate cancer.

[Risk-taking in adolescence: A neuroeconomics approach]. / Approche neuroéconomique de la prise de risque à l'adolescence.

OBJECTIVE: Risk-taking behaviors represent the main cause of morbi-mortality in adolescence. Here, we analyze their neural correlates, based on a neuroeconomics approach. This approach postulates that risk-taking behaviors result from multiple decision-making biases that impair the selection of the most appropriate action among alternatives based on their subjective evaluation. Specifically, we investigate three important domains in value-based decision-making: risk aversion, loss aversion and intertemporal choice. LITERATURE FINDINGS: First, when people have to make a decision between two rewarding options, they will usually prefer the more certain, even possibly lower, option - a phenomenon called "risk aversion". Yet adolescent people have been found to be less averse to risk than adults. This observation was linked to hypoactivation in (1) the anterior insula, involved in negative emotion such as fear and disgust and (2) the anterior cingular and the posterior ventromedial prefrontal cortices, involved in the monitoring of conflict and error detection. Second, people are generally described as being more sensitive to the possibility of losing objects than to that of gaining the same objects - "loss aversion". Here, we suggest that adolescents may be less averse to losses than adults when estimating the prospects of gaining and losing objects. Indeed, adolescent people have been found to be more affected by reward (e.g. euphoria or social integration consecutive to drug absorption) and less affected by punishment (e.g. malaise after drug consumption) than adults. Whereas the former process is subserved by hyperactivations in regions involved in reward evaluation such as the nucleus accumbens, the latter has been proposed to be subserved by hypoactivations in regions involved in negative emotions such as the amygdala or the insular cortex. This lower sensitivity to losses compared to gains in adolescents could be another important mechanism underlying risk-taking behaviors. A third dimension of adolescents' decision-making biases is temporality. It has been shown that adolescents favor immediate over delayed prospects, reflecting how future consequences of their decisions are heavily discounted. For example, adolescents can fail in projecting the future benefits of having safe sex - and thereby avoiding the risk of sexually transmitted disease or pregnancy - being more interested in the immediate reward of having romantic uninterrupted sexual intercourse. This impairment in inhibiting the choice of the early alternative could be related to the hypofunctionality of the lateral prefrontal cortex. Importantly, these three biases in the evaluation of decisions by adolescents may be related to the maturation of two neuronal systems. On the one hand, the early reorganization of dopaminergic neurons in the motivational system, due to the brutal secretion of sex hormones (mostly estrogens, testosterone and oxytocin) at the beginning of puberty, impels adolescents toward thrill seeking. On the other hand, the slow maturation of the cognitive control system, mostly exerted by the prefrontal cortex, implies that these impulses cannot be appropriately regulated. CONCLUSIONS: Two important neurodevelopmental mechanisms are thought to play a key role in the genesis of risk-taking behaviors in adolescence: the brutal secretion of sex hormones at the beginning of puberty and the delayed maturation of cognitive control. As such, these behaviors can be considered as inevitable, even if other factors, like sex, heredity and precariousness, can enhance their frequency. The implications of these conclusions for the prevention of risk-taking behaviors in adolescence are discussed.

[Best practice guide for radiation therapy of non-small cell bronchial cancers]. / Guide de bonne pratique pour la radiothérapie thoracique exclusive ou postopératoire des carcinomes non à petites cellules.

The objective was the drafting of a practical document intended for radiotherapists and radiophysicists, describing the technique of irradiation of a non small cell bronchial cancer. The good practices concern the care of patients affected by bronchial cancer localized in the thorax and inoperable or patients who must undergo postoperative irradiation. The document has been developed according to a methodology aiming to join the current scientific data from an analysis of the literature on the subject and the assessment of radiotherapists, radiophysicists, lung specialists and methodologists from Rhône-Alpes area. From the stages necessary for the good progress of a radiotherapy, the writers of this document proposed common definitions concerning the centering and the location of the zone to be treated, the calculation of the dose distribution, the preparation of the patient for the treatment, the treatment and the surveillance during the treatment. The recommendations of this guide took into account the peculiarities bound to the nature of the treated region and more particularly the lung heterogeneity, respiratory movements and the radiosensibility of healthy lung tissue. Even if the technical aspect of the radiotherapy was particularly developed, the interest accorded to patient information takes on all its importance for a therapeutic coverage of quality. The authors of the document wished that this Guide of Good Practices, which will be regularly updated, helps the radiotherapists and allows them to harmonize their practices.

[Interest of the radiotherapy-hormonotherapy association in the treatment of the high-risk prostate cancer]. / Apport de l'association radiothérapie externe-hormonothérapie dans le traitement du cancer de la prostate à haut risque.

Treatment of high-risk prostate cancer - localized or locally advanced - is based on the combination of external irradiation and hormonal treatment by LHRH analogue (aLHRH) according to the results of phases III randomized trials RTOG and/or EORTC trials. These trials show a significant improvement of overall or specific survival. Localized prostate cancer require 6-month complete androgen blockade, while locally advanced prostate cancer need a long-term hormonal treatment for a duration ranging from 2,5 to 3 years. Some trials, which have a long follow-up show that the risk of cardiovascular death is not significantly increased by hormonal treatment.

[Quantification of prostate movements during radiotherapy]. / Quantification des mouvements prostatiques lors de l'irradiation prostatique.

Decrease treatment uncertainties is one of the most important challenge in radiation oncology. Numerous techniques are available to quantify prostate motion and visualise prostate location day after day before each irradiation: CT-scan, cone-beam-CT-Scan, ultrason, prostatic markers... The knowledge of prostate motion is necessary to define the minimal margin around the target volume needed to avoid mispositioning during treatment session. Different kind of prostate movement have been studied and are reported in the present work: namely, those having a large amplitude extending through out the whole treatment period on one hand; and those with a shorter amplitude happening during treatment session one the other hand. The long lasting movement are mostly anterior-posterior (3 mm standard deviation), secondary in cranial-caudal (1-2 mm standard deviation) and lateral directions (0.5-1 mm standard deviation). They are mostly due to the rectal state of filling and mildly due to bladder filling or inferior limbs position. On the other hand, the shorter movement that occurs during the treatment session is mostly variation of position around a steady point represented by the apex. Ones again, the rectal filling state is the principle cause. This way, during the 20 minutes of a treatment session, including the positioning of the patient, a movement of less than 3 mm could be expected when the rectum is empty. Ideally, real time imaging tools should allow an accurate localisation of the prostate and the adaptation of the dosimetry before each treatment session in a time envelope not exceeding 20 minutes.

[Retrospective analysis of 108 ductal carcinomas in situ of the breast treated by radiosurgery association]. / Analyse rétrospective de 108 carcinomes canalaires in situ mammaires traités par association radiochirurgicale.

PURPOSE: To evaluate survival and prognostic factors of 108 patients with clinically or mammographically detected ductal carcinoma in situ (DCIS), treated from 1980 to 1996 by complete local excision followed by external irradiation. PATIENTS AND METHODS: The median age was 51 (range 37-80). All the patients underwent surgery consisting of a wide resection of the mammary gland harbouring the tumour. The surgical specimens were sent to the pathologists to get information on histology and margin clearance; all the slides were reviewed by one of us to assess the tumoral diameter. External beam therapy was delivered within 8 weeks after surgery. The prescribed irradiation dose was 50 Gy in 25 fractions to be given in 5 weeks. The median duration of follow-up was 93 months (range 40-173). RESULTS: There were nine patients with local recurrence (8.3%); three patients had local recurrence of DCIS and six patients developed invasive breast cancer. The treatment of local recurrence consisted of mastectomy with or without axillary dissection (eight cases) and quadrantectomy (one case). The 5-year and 10-year ipsilateral recurrence-free rate was respectively 92 and 89%. The 10-year cause specific survival was 100%. In univariate analysis, size>or=10 mm, age<45 years old and margin status were significant P=0,02, P=0,03, P=0,005; margin status was significant in multivariate analysis (P<0,02). CONCLUSION: These results are in keeping with those of the literature. They could be improved by the mass screening campaign, which is going on since January 1990 among women aged 50-74 years.