[Anorexia nervosa in the light of neurocognitive functioning: New theoretical and therapeutic perspectives]. / L'anorexie mentale à la lumière du fonctionnement neurocognitif : nouvelles perspectives théoriques et thérapeutiques.

INTRODUCTION: Anorexia nervosa is a serious psychiatric disorder, for which very few validated therapeutic strategies exist. The specific sociocognitive style of anorexic patients has already been described in the 1960s: it involves a concrete style with abstraction difficulties. Current neuropsychological tests have contributed to a more precise definition of these difficulties. NEUROPSYCHOLOGICAL DATA: IS THERE A SPECIFIC COGNITIVE PROFILE?: Contrary to common beliefs, these patients' intellectual performances are not superior to those of the general population. However, detailed comparisons of profiles on the Weschler Scales suggest difficulties in synthesizing information and better abilities in concrete problem solving. EXCESSIVE ATTENTION TO DETAILS: The dominant hypothesis concerning the attentional dimension is the existence of a weakness in central coherence, resulting in superior detail processing and a weakness in global integration. This trend appears to be stable even after the normalization of nutritional status. IMPAIRED COGNITIVE FLEXIBILITY: The impairment of set-shifting abilities leads to rigidity, expressed by inflexibility and perseveration, both in reasoning and behaviour. This reduced cognitive flexibility appears to persist after recovery, and may constitute a familial trait. In addition, this likely endophenotype seems to be independent from obsessional traits. CONTROVERSIAL SOCIAL SKILL: Alexithymia is frequently described in anorexic individuals. It is the verbal description of feelings which seems to be particularly impaired. It may explain underlying difficulties in empathy. Indeed, these subjects have lower scores on emotional tests drawn from the theory of mind. These cognitive abnormalities are well documented in pervasive developmental disorders. NEUROANATOMICAL DATA: NEUROIMAGING IN SUPPORT OF LIMBIC AND FRONTO-STRIATAL ABNORMALITIES: Evidence from neuroimaging suggests abnormalities in cortical and subcortical structures, involving the temporal and orbito-frontal lobes. Various functional hypotheses are formulated, involving fronto-striatothalamic circuits, amygdala or insula. IS ANOREXIA NERVOSA A DEVELOPMENTAL DISORDER?: Pervasive developmental disorders are over-represented among anorexic subjects in comparison to the general population. Conversely, restrictive and selective eating disorders are more frequent among individuals presenting an autistic spectrum disorder. THERAPEUTIC IMPLICATIONS AND FUTURE DIRECTIONS: In view of the common cognitive and neuroanatomical data that are found in anorexia nervosa and neurodevelopmental disorders, we adhere to the hypothesis that anorexia nervosa may be similar to a neurodevelopmental disorder. Clinical observations suggest that this hypothesis may be especially relevant in the early forms of anorexia nervosa. These cognitive data confirm the potential relevance of new therapeutic modalities such as cognitive remediation. Initial results from its application to anorexia nervosa seem promising. CONCLUSION: A review of the recent literature highlights the possible existence of a developmental impairment of cortical and subcortical structures, associated with specific abnormalities in cognitive development such as a weakness in central coherence, reduced set-shifting ability and poor social skills. On this basis, cognitive remediation may be a promising therapeutic innovation.

[Cognitive remediation therapy for children and adolescents with anorexia nervosa in France: an exploratory study]. / Évaluation d'un programme de remédiation cognitive au sein d'un groupe d'enfants et d'adolescents anorexiques français: étude exploratoire.

OBJECTIVE: Cognitive remediation therapy (CRT) seems to be increasingly interesting in the treatment of anorexia nervosa for adult patients. We attempted to apply this support to a group of young inpatients, initially to assess its feasibility and acceptability, and then to improve its content for therapeutic application and future research. METHODS: Ten 12- to 17-year-old inpatients with primary DSM-IV diagnosis of anorexia nervosa participated in a 10-week intervention program with a one-hour group session of CRT per week. All 10 patients were assessed before the intervention and those who completed the 10 sessions were assessed after. Assessment included a clinical examination by a psychiatrist, a battery of clinical inventories, and set-shifting tests. Moreover, each patient wrote a letter providing feedback on the intervention for subsequent analysis. RESULTS: Only two patients completed all 10 sessions, the other eight who were discharged from the hospital in the meantime could not attend the sessions for practical reasons. After the 10 sessions, an improvement in BMI and in measured levels of some psychopathological symptoms was observed in our two patients. Most neuropsychological task performances were improved after cognitive remediation. Feedback from the 10 patients was generally positive. CONCLUSION AND IMPLICATIONS FOR PRACTICE: This preliminary investigation suggests that cognitive remediation therapy is acceptable and feasible in this population. Replication of these findings requires a larger sample, improvement of the trial design, more sensitive measures, and another training format to avoid loss of so many participants.

Family therapy in the treatment of adolescent anorexia nervosa: current research evidence and its therapeutic implications.

From the outset, the systemic and family movement has expressed an interest in eating disorders, more specifically anorexia nervosa, establishing causal links between family functioning and aetiology and advocating family therapy as the treatment of choice for this disorder. Because of high consistency between its explanatory and therapeutic dimensions, this model continues to dominate our conceptualizations and clinical practice, in spite of a lack of empirical support. This article summarizes present empirical evidence concerning both family functioning (explanatory dimension) and the effectiveness of family therapy (therapeutic dimension) in anorexia nervosa, and describes resulting changes in theoretical and clinical perspectives. A model of evidence-based family therapy is presented and several unresolved issues are raised. Overall, this overview of the literature supports the use of therapeutic models that are more flexible and normative, less guilt-inducing, more diversified (eclectic and integrative), and more rooted in the empirical literature.

[Münchhausen syndrome by proxy]. / Syndrome de Münchhausen par procuration.

Münchhausen syndrome by proxy is a factitious disorder, a disease produced or simulated by a parent, the mother in most cases. Clinical presentation is miscellaneous (factitious bleeding, epilepsy, apnea are frequent) and unusual. Physicians participate in the abuse by their therapeutic and diagnostical measures. It is very important to think about this diagnostic in any ambiguous situation in order to evaluate and protect the child.

[Psychopathology of children reared in lesbian families: literature review]. / Psychopathologie des enfants élevés en milieu homoparental lesbien: revue de la littérature.

For several years, a growing number of children raised in lesbian families have been noticed. Even if this number is not really known, it appears clearly that more and more psychiatrists will have to care for children which will present this family configuration. The problem then is to know if this type of education has an incident on the psychopathology of children or not. The purpose of this article is not to give answer or to take side but just to help physicians to make a point of what is known about this subject in international literature.

Lack of association of the dopamine transporter gene in a French ADHD sample.

Discrepancies in the role of the 40 bp VNTR polymorphism of the dopamine transporter gene (DAT1) in attention-deficit hyperactivity disorder (ADHD) could be due to various sources of genetic or phenotypical heterogeneity. We therefore analyzed a sample of 146 ADHD children and their parents, with a transmission disequilibrium test (TDT) design, assessing age, inattention, and hyperactivity dimensions and total score of the ADHD Rating Scale, the number of errors and the total score at Stroop Color-Word test, and the total score at the Trail Making Test. The TDT for 10-repeat (10-R) allele shows a perfect lack of transmission bias (Mc Nemar chi(2) = 0) and PBAT analyses showed no role of this polymorphism for any of the studied endophenotypes. Lack of statistical power is always a possibility, but with a sample size above the average of the majority of previous studies, and an odds ratio (number of transmitted versus untransmitted 10-R allele) of 1.00 exactly, this possibility may be considered as not very likely.

Pharmacogenetics of methylphenidate response in attention deficit/hyperactivity disorder: association with the dopamine transporter gene (SLC6A3).

Pharmacogenetic studies investigating the 40-bp VNTR polymorphism at SLC6A3 and methylphenidate response have shown conflicting results and large differences in study design and efficacy endpoints. Our objective was to investigate the relation between the 3'-VNTR at SLC6A3 and variability in methylphenidate response in a sample of 141 ADHD children and adolescents, assessed before and after methylphenidate treatment with both clinical and neuropsychological outcome measures. 10-R homozygotes were significantly overrepresented in the low response group, but no genotype effect was shown in cognitive variables improvement. A meta-analysis of pharmacogenetic studies with comparable data (responders vs. non-responders) on a total of 475 subjects showed a significant association between the 10-10 genotype and low rates of methylphenidate response (mean Odds Ratio = 0.46; 95% CI [0.28-0.76]). Heterogeneity between these studies did not reach a significant level but, as publications with different endpoints were excluded from this meta-analysis, our results do not rule out a possible influence of study design.

Switching to the bingeing/purging subtype of anorexia nervosa is frequently associated with suicidal attempts.

OBJECTIVE: Anorexia nervosa has the highest suicide mortality ratio of psychiatric disorders, suicide being associated with many factors. We assessed the first lifetime occurrence of these factors taking into account their possible overlap. METHOD: Three hundred and four in- and out-patients with anorexia nervosa (DSM-IV) were systematically recruited in three hospitals of Paris suburbs, between December 1999 and January 2003. Patients were assessed by a face-to-face interview (DIGS). Current eating disorder dimensions were measured, and patients interviewed by a trained clinician to assess minimal BMI and, retrospectively, the age at which anorexia nervosa, major depressive disorder, anxiety disorders and switch to bingeing/purging type occurred for the first time, if applicable. RESULTS: Major depressive disorder (p<0.001) and subtype switch from the restrictive to the bingeing/purging type (p<0.001) were the two factors significantly more frequently occurring before suicidal attempts, and remained involved when a multivariate analysis is performed, whether syndromic or dimensional measures are being used. Taking into account lifetime occurrence with a survival analysis, the switch to bingeing/purging type of anorexia appears as a major predictive factor, with a large increase of the frequency of suicidal attempts (OR=15) when compared to patients with neither major depressive disorder nor bingeing/purging type. CONCLUSIONS: Bingeing/purging type of anorexia nervosa is largely associated with suicidal attempts, and may deserve specific attention. If confirmed on a prospectively designed study, these results would argue for early detection and/or more intensive and specific therapeutic intervention on this aspect of bingeing and purging behaviors.

[Medical treatments of hyperactive child: about the new pharmaceutical forms of methylphenidate marketed in France]. / Traitements médicaux de l'enfant hyperactif: à propos des deux nouvelles formes de méthylphénidate commercialisées en France.

Multimodal treatment of hyperactive child includes psychostimulant medication, methylphenidate (MPH) marketed in France in its short-acting form since about ten years. We report our clinical experience about the first fifty methylphenidate responders who received one of the two sustained-release forms available since summer 2004, tablets of oros-methyphenidate (Concerta LP) or microgranule-filled capsules (Ritaline LP).

Meta-analysis of family-based association studies between the dopamine transporter gene and attention deficit hyperactivity disorder.

INTRODUCTION: Molecular genetic research has mainly focused on the D4 dopamine receptor (DRD4) and the dopamine transporter (DAT) genes in attention-deficit hyperactivity disorder (ADHD). A recent meta-analysis showed that the DRD4 gene has a significant role in the vulnerability to ADHD. OBJECTIVES: With an equal number of positive and negative association studies between the 10-repeat of the DAT gene and ADHD, a meta-analysis is required for this other candidate gene. METHODS: We re-analysed the 13 published family-based association studies between ADHD and the DAT gene. Following recent recommendations, different biases were specifically assessed, such as the sample-size effect and the time effect. RESULTS: The meta-analysis showed no significant association between ADHD and the DAT gene (P = 0.21), but an important between-samples heterogeneity (P = 0.0009). Odds ratios above 1 are mostly observed in studies with a small number of informative transmissions, and decrease with larger sample size. CONCLUSIONS: Contrary to what was found for the DRD4 gene, the 10-repeat allele of the DAT gene has at most a minor role in the genetic susceptibility of ADHD. The different biases detected herein probably explain the initial impression of a significant impact of the DAT gene on hyperactivity.

[Meta-analysis of candidate genes in attention-deficit hyperactivity disorder]. / Meta-analyse des gènes candidats dans le trouble déficit attentionnel avec hyperactivité (TDAH).

Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder observed during childhood, detected in 3% to 5% of school-age children. The disorder is characterised by marked inattention, hyperactivity, and impulsiveness. In most cases, symptoms can be treated by catecholamine-releasing drugs, such as methylphenidate. Children with ADHD are at higher risk for substance abuse and oppositional, conduct and mood disorders. Familial and adoption studies shed light on the genetic vulnerability of ADHD. Twin studies estimated the broad heritability to range between 40% and 90%. The mode of transmission is yet unknown, but is likely polygenic. Molecular genetic studies in ADHD should contribute to a greater understanding of the pathophysiology of the disorder (genetics of the vulnerability), and could help to select a more rational type of treatment (pharmacogenetic). Family-based association studies already performed are reviewed in this manuscript. Association studies, using haplotype relative risk (HRR) or transmission disequilibrium test (TDT) have focused on candidate genes which code for proteins potentially involved in the etiopathogenesis of the disorder. Genes involved in dopamine, serotonin, and noradrenalin systems have thus been assessed for their role in core features of ADHD, such as motor overactivity, inattention, and impulsiveness. According to a meta-analysis, the DAT1 gene, an obvious candidate gene in ADHD vulnerability, does not appear to be involved (OR = 1.13, p = 0.21). On the other hand, DRD4 (OR = 1.26, p = 0.01) and DRD5 (OR = 1.4, p = 0.01) are significantly associated to ADHD according to the present meta-analysis, confirming previous ones. Recent studies showed a trend for an association between one allele of the 5-HTT (considering case-control studies) and DBH (OR = 1.27, p = 0.06) genes and ADHD, but these positive findings have to be replicated. ADHD is a complex disorder with potentially many different risk factors. Genetic and phenotypic heterogeneity could explain why some association studies are positive, whereas others are negative. For instance, different developmental pathways are likely to lead to similar clinical outcomes. More clear-cut phenotypes, such as ADHD with conduct disorder, or ADHD with bipolar disorder, could be more homogenous, the genes involved being therefore more easy to detect. These phenotypes are beginning to be specifically studied in molecular genetics. In addition, the development of pharmacogenetics could help to identify predictors of clinical response for a specific type of treatment, which would be clearly helpful in clinical practice.

[Fragile X syndrome and very early onset schizophrenia: a female case study]. / Syndrome de l'X fragile et schizophrénie à début très précoce : à propos d'un cas féminin.

Genotype-phenotype relationship studies for psychiatric disorders in females carrying fragile X syndrome full mutation and premutation underline association with schizo-affective disorders. In female children with X fragile full mutation, only behavioural symptoms and no standardised psychiatric disorders have been systematically explored. Therefore, we report the case of a nine-year-old girl carrying the fragile X syndrome full mutation with a comorbid childhood onset schizophrenia (COS), and of her mother carrying the fragile X syndrome premutation and a comorbid schizotypal personality disorder. The impact of these associations is discussed regarding the recent literature in chromosome anomalies in COS.

[Symptom variations in ADHD: importance of context, development and comorbidity]. / Variations dans l'expression clinique du trouble déficit attentionnel/hyperactivité (TDAH): rôle du contexte, du développement et de la comorbidité thymique.

Attention-deficit hyperactivity (ADHD) is a common disorder in school-aged children and is associated with significant impairment in social and academic functioning. Its recognition is based on congruent information from different sources, because most ADHD children and adolescents are not completely aware of impairments caused by inattention and/or hyperactivity/impulsivity. Fluctuations in symptom expression may complicate the diagnosis: during clinical examination or tests sessions, ADHD symptoms may be less severe than usual or completely absent. This review examines variations in ADHD symptoms due to environmental context, internal state, circadian factors, development, psychiatric comorbidity and discusses their clinical relevance. Generally, ADHD symptoms are pervasive and identified in different areas of functioning. Despite their chronicity, they show a relative context-dependency. An unfamiliar environment or situation may lessen symptoms. The same happens in dual relations or in calm settings, when the child receives attention and positive reinforcement from the adult. On the contrary, the classroom situation with its high stimulation level (noise, visual distractors, large class size) is likely to reveal or accentuate instability, impulsivity and inattention. Independently from objective symptom fluctuations, the impact of ADHD symptoms, and their consequences on self-esteem may also vary with the degree of environmental mismatch. Recent research in experimental psychology also draws attention to the motivational state of ADHD children: preference for immediate gratification and delay aversion may explain why most of them show satisfactory attentional capacities in certain activities (for instance video games or TV), while showing impairment in school work or in other effortful tasks. The diagnosis of the full ADHD syndrome requires significant impact on functioning in at least two areas. Some children with "situational" ADHD are impaired either in school setting or exclusively at home. Manuzza et al. report long-term outcome of "situational" versus "pervasive" ADHD. School-ADHD, in opposition to home-ADHD shows similarities with the full blown syndrome, as regards proportion of anti-social personality disorder, psycho-social functioning and academic/professional achievements. Moderate seasonal variations have also been identified with less ADHD symptoms in August. This result is likely to reflect a better fit between individual characteristics and environmental demands during school holidays rather than neurobiological changes, as there are no convincing arguments for seasonal fluctuations of serotoninergic tone in ADHD. Another cause for variations in ADHD symptom expression may be the co-occurrence of a mood disorder. Relationships between early-onset mania and ADHD are discussed. The appropriate definition of prepubertal mania is still in debate; its recognition is hindered by symptom overlap and high level of comorbid conditions. Chronic emotional dysregulation with irritability and frequent temper tantrums, sometimes viewed as characteristics of early-onset mania, might reflect a--possibly severe--sub-type of ADHD rather than a prodrome of bipolarity. A marked cyclicity of symptoms, with periodic accentuation of ADHD and mood symptoms, requires careful monitoring and systematic analysis of comorbid conditions. Clarification of the complex interrelations between ADHD and bipolar disorder will be obtained from long-term studies.

[Depression in the child: Clinical and psychopathological aspects]. / La depression chez l'enfant: aspects cliniques et psychopathologiques.

The present work is exclusively about depressions in childhood till the end of latency (11--12 years old children). It serves a double purpose: to try and show that children from their earliest childhood can be subject to feelings of sadness, moodiness, dismay, self-depreciation; to facilitate, through a better clinical and psychological knowledge, diagnoses in (cases of) depressions. In the first part, we shall study the different clinical forms of depressive states, their factors and their evolution. Three cases of personnal observations will illustrate those theoretic data. The relations between suicide and depression are introduced in the second part of this work. Finally, the authors will tell about the main psychanalytic works which permit to progress towards the recognition of the central function of the depressive phenomena in the structure of a personnality.

[Post emotional syndromes (author's transl)]. / Les syndromes post-émotionnels

On the basis of ten clinical cases of post emotional shock, the following aspects are discussed: the causal emotion and its characteristics, its psychological repercussions and the mechanisms involvent, the clinical patterns observed, both somatic and psychic, and their interpretation. Attention is called to the consequences of such emotions from the forensic view-point and the need to ascertain and specify the nature and intensity of the emotional trauma and the actual state of anxiety. Emphasis is laid on the difficulty of making expert appraisals and fixing equitable compensations, as experts differ and their approaches to the problem and also because of the functional character of sequela and their varying degree of severity.

[Animals and their masters. Psychological and psychopathological aspects]. / Les animaux et leurs maitres. Aspects psychologiques et psychopathologiques.

Animals have always occupied a privileged place beside man and with him form a couple, a duality. In the first part the authors study the psychology of the adopted animal. Then they look at greater length into the personality of his owner, with particular insistence on the reasons for acquiring it, on the choice of animal (dog, cat, horses), on the part it plays in the life of its master, and on the latter's reaction at his companion's death. They also tackle the problem of man's abnormal behaviour in relation to animals, especially bestiality.

[Vagrancy: psychological and psychopathological aspects]. / Le vagabondage: aspects psychologiques et psychopathologiques.

The authors, after defining the words "vagrancy" and "vagrant", explore their semantical field and try to specify differences in respect of neighbouring words, often confused with them. An historical sketch of vagrancy, from antiquity to the present era, is depicted. There after, the authors state the evolution of theories of vagrancy, from the biological, psychological, psychiatrical and sociological points of view. The last part of the paper considers psychopathology of vagrancy, specially in psychoanalytical and phenomenological approaches, and problems of rehabilitation.

[Apropos of mother-child hospitalizations: mother-child hospitalization in a child psychology service]. / A propos des hospitalisations mère-enfant: l'hospitalisation mère-enfant dans un service de psychopathologie de l'enfant.

Mother-child hospitalization is still rarely practiced in child psychiatric services. The experience of this kind of care in the child and adolescent psychopathology service in the Herold Hospital (Paris), however, demonstrates its interest. It permits one to respect the bond of attachment and proves to be a useful instrument of psychiatric evaluation of children, particularly in greater diagnostic precision to which the observation of the mother-child unit also contributes. The conjoint hospitalization, however, involves some risks, which can be anticipated in pre-hospitalization work up: repercussion on the family, difficulties in the functioning of the care taking team, and especially the impact on the mother of the hospitalization which creates a real crisis situation which must be handled in order to be able to use the maturative possibilities.

[Cardiovascular risks and management during Attention Deficit Hyperactivity Disorder treatment with methylphenidate]. / Risques cardiovasculaires et conduite à tenir dans le traitement du trouble déficit de l'attention/hyperactivité avec le méthylphénidate.

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common of the pediatric neuropsychiatric disorders. Methylphenidate is an important element of therapeutic strategies for ADHD. Clinicians are interested in the safety of methylphenidate. Because this drug raises heart rate and blood pressure, concerns have been raised about its cardiovascular safety. Concerns were based on case reports of sudden cardiac death in methylphenidate users, plausible pharmacological pathways involving well-established stimulant effects on heart rate and blood pressure. Until recently, data were limited to a number of observational studies too small to examine serious cardiac events. In the past two years, large retrospective, population-based cohort studies were performed. These studies did not show any evidence that methylphenidate was associated with an increase in risk of myocardial infarction, sudden cardiac death, or stroke. Treatment of children with methylphenidate is not significantly associated with an increase in the short term or mid-term risk of severe cardiac events. For many, available data now will be seen as reassuring. But gaps persist in the methodical and comprehensive assessments of the safety of methylphenidate. Analyses cannot be generalized to children with long-term use of stimulants. Furthermore, long-term effects of slight increases in heart rate or blood pressure are unknown. Stimulant administration continues to have a detectable adrenergic effect even after years of treatment. In the MTA study, greater cumulative stimulant exposure was associated with a higher heart rate at years 3 and 8. Although less severe, such adverse cardiac events are nonetheless alarming to patients. This adrenergic effect may have clinical implications, especially for individual patients with underlying heart abnormalities and it deserves further investigation. More research is necessary to optimize a safe use of methylphenidate regarding its cardiovascular effects. In light of the controversies surrounding the increase in the number of children being diagnosed with ADHD, the broad use of methylphenidate in these patients, and cardiovascular concerns about it, this article addresses topics of clinical significance. For ease of use by practitioners, the article summarizes the guidelines stated by the European Medicines Agency over the appropriate pretreatment evaluation and cardiovascular assessment. It advocates a thorough history and physical examination before initiating methylphenidate to treat patients with ADHD, with an emphasis on the identification of risk factors for sudden death. A cardiac sub-specialist consultation is mandatory in case of history or physical examination findings. In other cases, an electrocardiographic screening is recommended in order to check out previously unrecognized heart disease.