ABSTRACT
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.
Subject(s)
Anorexia Nervosa/therapy , Cognitive Behavioral Therapy/methods , Psychotherapy, Group/methods , Adolescent , Anorexia Nervosa/psychology , Body Image , Body Mass Index , Child , Feasibility Studies , Female , Hospitalization , Humans , Male , Neuropsychological Tests , Patient Acceptance of Health Care/psychology , Patient Satisfaction , Personality Inventory , Set, PsychologyABSTRACT
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.
Subject(s)
Anorexia Nervosa/diagnosis , Anorexia Nervosa/psychology , Cognition Disorders/diagnosis , Cognition Disorders/psychology , Adolescent , Anorexia Nervosa/physiopathology , Anorexia Nervosa/therapy , Attention/physiology , Brain/physiopathology , Cognition Disorders/physiopathology , Cognition Disorders/therapy , Comprehension/physiology , Female , Humans , Neuropsychological Tests , Problem Solving/physiology , Social Skills , Young AdultABSTRACT
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.
Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Central Nervous System Stimulants/adverse effects , Central Nervous System Stimulants/therapeutic use , Death, Sudden, Cardiac/etiology , Methylphenidate/adverse effects , Methylphenidate/therapeutic use , Myocardial Infarction/chemically induced , Stroke/chemically induced , Blood Pressure/drug effects , Child , Cooperative Behavior , Drug Monitoring , Guideline Adherence , Heart Rate/drug effects , Humans , Interdisciplinary Communication , Long-Term Care , Referral and Consultation , Risk FactorsABSTRACT
There are no official guidelines for the treatment of anorexia nervosa in young patients. Some recommendations have been proposed by a group of British experts (N.I.C.E., 2004), based on results from controlled studies. Our inpatient care unit takes into account the different dimensions of anorexia nervosa in this subgroup of young patients and proposes an integrated approach including medical care, nutritional care, and psychological care, as suggested by the N.I.C.E. recommendations. We attempt to take into account variables that are unique to these young patients. More specifically, we insist on weight restoration that will permit adequate growth and we do not systematically separate the patient from his or her family. In addition, family therapy or counseling is systematically provided. The aim of this approach is to support parents, to provide psychoeducational guidance, and to help the family acquire new behaviors and new ways of understanding the eating disorder. Most patients are treated on an outpatient basis, but inpatient care is offered when the patient displays severe medical conditions or a severe comorbid psychiatric illness. Anorexia nervosa is a protracted disorder that requires multidisciplinary outpatient medical follow-up, including the intervention of a general practitioner and a psychiatric team.
Subject(s)
Anorexia Nervosa/therapy , Hospitalization , Patient Care Team , Psychiatric Department, Hospital , Psychotherapy/methods , Adolescent , Ambulatory Care , Child , Combined Modality Therapy , Cooperative Behavior , Evidence-Based Medicine , Family Practice , Family Therapy , Humans , Interdisciplinary Communication , Nutrition Assessment , Nutritional Support , Practice Guidelines as Topic , Psychoanalytic Therapy , Psychotherapy, Group/methods , Weight GainABSTRACT
PURPOSE: The aim of this study was to investigate the use of psychotropic medications for both labeled and off-labeled indications in a French paediatric teaching hospital. METHODS: A prospective analysis of all psychotropic drug prescriptions was conducted during a 6-month interval. Details were recorded from the computerized prescription order entry system. They included demographic data (sex, age and weight) and psychotropic medications (name, dosage, schedule, route of administration and indication). The physicians specified the indication when prescribing the psychotropic medication. All prescriptions were assessed for off-label use. Off-label prescriptions were defined as: use of a different dose or dose schedule, use for an indication not included in the license or approved for adults only, drug use outside the age range of the product license, use of medicines for which no paediatric information was available, use when the product was contraindicated, use of drug preparations that were manufactured by the hospital pharmacy, use of licensed drugs that were modified by the hospital pharmacy and use of new drugs available under a special manufacturing license. Each prescription was compared with data available in the National French Formulary. RESULTS: A total of 1629 drug prescriptions were written for 472 patients. Sixty-eight percent of all drug prescriptions were for off-label uses: indication not included in the license or approved for adults only in 40%, no paediatric information available in 37%, different dose or dose schedule in 7%, licensed drugs that were modified by the hospital pharmacy in 5%, administration to children outside the age range of the product license in 4%, drug preparations that were manufactured by the hospital pharmacy in 4%, contraindication in 2% and new drugs available under a special manufacturing license in 1%. Sixty-six percent of the patients were prescribed a psychotropic drug in an off-label manner. Over half of the off-label prescriptions were given to adolescents (62%), followed by children (29%), infants (8%) and neonates (1%). The percentage of off-label prescriptions by age was: neonates 91%; adolescents 74%; children 59% and infants 58%. The percentage of off-label prescriptions by medication class are presented in decreasing order of prescription frequency: anxiolytics 65%; antipsychotics 69%; antidepressants 92%; antiepileptics 51%; stimulants 30%; antiparkinsonians 100% and hypnotics 100%. The 5 drugs most commonly prescribed off label were risperidone (12%), clobazam (12%), amitriptyline (11%), hydroxyzine (10%) and diazepam (7%). Nearly half (47%) of all off-label prescriptions were associated with 3 indications: anxiety (24%), disruptive behaviour (12%) and pain (11%). CONCLUSION: The high rates of off-label prescription documented here and elsewhere highlight the need for further controlled clinical trials to evaluate the risks and benefits of psychotropic medication in children and adolescents.
Subject(s)
Mental Disorders/drug therapy , Off-Label Use/statistics & numerical data , Psychotropic Drugs/therapeutic use , Adolescent , Child , Child, Preschool , Drug Administration Schedule , Female , Hospitals, Pediatric , Hospitals, Teaching , Humans , Infant , Infant, Newborn , Male , Medical Records Systems, Computerized , Paris , Prospective Studies , Psychotropic Drugs/administration & dosageABSTRACT
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.
Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Central Nervous System Stimulants/therapeutic use , Dopamine Plasma Membrane Transport Proteins/genetics , Methylphenidate/therapeutic use , Pharmacogenetics/methods , Adolescent , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/genetics , Chi-Square Distribution , Child , DNA/genetics , DNA/isolation & purification , Genotype , Homozygote , Humans , Meta-Analysis as Topic , Microsatellite Repeats , Odds Ratio , Polymorphism, Genetic , Probability , Treatment OutcomeABSTRACT
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.
Subject(s)
Family , Homosexuality, Female , Mental Disorders/epidemiology , Adolescent , Adult , Age Factors , Child , Child Abuse, Sexual , Child, Preschool , Cohort Studies , Divorce , Epidemiologic Studies , Family/psychology , Female , Follow-Up Studies , Heterosexuality , Homosexuality, Male , Humans , Insemination, Artificial , Longitudinal Studies , Male , Mother-Child Relations , Prejudice , Psychological Tests , Risk Factors , Sexual Behavior , Single-Parent Family , Surveys and Questionnaires , Time FactorsABSTRACT
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.
Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Dopamine Plasma Membrane Transport Proteins/genetics , Genetic Predisposition to Disease , Adolescent , Alleles , Attention Deficit Disorder with Hyperactivity/diagnosis , Chi-Square Distribution , Child , Confidence Intervals , Female , France , Humans , Linkage Disequilibrium , Male , Microsatellite Repeats , Mothers/statistics & numerical data , Odds Ratio , Polymorphism, Genetic , Severity of Illness IndexABSTRACT
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.
Subject(s)
Munchausen Syndrome by Proxy/diagnosis , Adult , Child , Diagnosis, Differential , Female , Humans , Mother-Child Relations , Munchausen Syndrome by Proxy/psychologyABSTRACT
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.
Subject(s)
Anorexia Nervosa/therapy , Family Therapy , Adolescent , Anorexia Nervosa/psychology , Evidence-Based Medicine , Family Therapy/methods , Female , Humans , Male , Self Efficacy , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Early recognition of attention-deficit/hyperactivity disorder (ADHD) may improve the educational and psychosocial outcome of most affected children. To date, factors associated with diagnostic delay of ADHD have not specifically been addressed. Aims of this study were to evaluate the mean diagnostic delay (time between first consultation and definite diagnosis) in a clinical sample of French children with ADHD referred to an outpatient university clinic, and to determine associated factors. METHOD: A total of 129 consecutively referred ADHD patients aged 6-16 years. A detailed history of the children was obtained from their parents. The Kiddie-SADS-PL, the ADHD-Rating Scale, and the Clinical Global Impression Scale were used for clinical assessment. RESULTS: Mean diagnostic delay was 32.89 months. A previous suspicion of ADHD by any health care professional, therapist or teacher was significantly associated with a reduced diagnostic delay. Co-morbidity with anxiety/depressive disorders and previous contact with a mental health professional were associated with a significant delay in diagnosis. CONCLUSION: Delay in diagnosis of ADHD in France is among the longest reported. Children with co-morbid anxiety or depressive disorders are particularly at risk of having a significant delay in the diagnosis. Health professionals, therapists and teachers may play a relevant role to accelerate the diagnostic procedure.
Subject(s)
Attention Deficit Disorder with Hyperactivity/diagnosis , Early Diagnosis , Health Services Needs and Demand , Referral and Consultation , Adolescent , Child , Female , France , Humans , Linear Models , Male , Multivariate Analysis , Referral and Consultation/statistics & numerical data , Time FactorsABSTRACT
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.
Subject(s)
Anorexia Nervosa/psychology , Bulimia Nervosa/psychology , Suicide, Attempted/psychology , Adolescent , Adult , Anorexia Nervosa/diagnosis , Anorexia Nervosa/mortality , Anxiety Disorders/diagnosis , Anxiety Disorders/mortality , Anxiety Disorders/psychology , Body Mass Index , Bulimia Nervosa/diagnosis , Bulimia Nervosa/mortality , Comorbidity , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/mortality , Depressive Disorder, Major/psychology , Female , Humans , Impulsive Behavior/diagnosis , Impulsive Behavior/mortality , Impulsive Behavior/psychology , Interview, Psychological , Male , Multivariate Analysis , Paris , Regression Analysis , Retrospective Studies , Risk Factors , Suicide, Attempted/prevention & control , Suicide, Attempted/statistics & numerical data , Survival AnalysisABSTRACT
OBJECTIVE: Preliminary evidence suggests a comorbidity between attention-deficit/hyperactivity disorder (ADHD) and obesity. This study was carried out to identify the clinical characteristics of obese adolescents with a higher probability of ADHD and advance the understanding of the potential factors underlying the comorbidity between obesity and ADHD. We evaluated the association between ADHD symptoms and bulimic behaviors, depressive and anxiety symptoms, degree of obesity, pubertal stage, age and gender in a clinical sample of obese adolescents. DESIGN: Cross-sectional study. SUBJECTS: Ninety-nine severely obese adolescents aged 12-17 years. MEASUREMENTS: Subjects filled out the Bulimic Investigatory Test, Edinburgh, the Beck Depression Inventory and the State-Trait Anxiety Inventory for Children. Their parents completed the Conners Parent Rating Scale, which assesses ADHD symptoms. The degree of overweight was expressed as body mass index-z score. Puberty development was clinically assessed on the basis of Tanner stages. RESULTS: Bulimic behaviors were significantly associated with ADHD symptoms after controlling for depressive and anxiety symptoms. The degree of overweight, pubertal stage, age and gender were not significantly associated with ADHD symptoms. CONCLUSION: Obese adolescents with bulimic behaviors may have a higher probability to present with ADHD symptoms independently from associated depressive or anxiety symptoms. The degree of overweight, pubertal stage, age and gender might not be useful for detecting obese adolescents with ADHD symptoms. Therefore, we suggest systematic screening for ADHD in obese adolescents with bulimic behaviors. Further studies are needed to understand which specific dimension of ADHD primarily accounts for the association with bulimic behaviors. Future research should also investigate the causal link between bulimic behaviors and ADHD and explore potential common neurobiological alterations. This may lead to a better understanding of the effectiveness of stimulants for the treatment of bulimic behaviors in obese subjects.
Subject(s)
Attention Deficit Disorder with Hyperactivity/psychology , Bulimia/psychology , Obesity/psychology , Adolescent , Anthropometry/methods , Anxiety/psychology , Body Constitution , Child , Cross-Sectional Studies , Depression/psychology , Female , Humans , Male , Psychiatric Status Rating Scales , PubertyABSTRACT
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).
Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Central Nervous System Stimulants/therapeutic use , Methylphenidate/therapeutic use , Central Nervous System Stimulants/administration & dosage , Child , Delayed-Action Preparations , Female , France , Humans , Male , Methylphenidate/administration & dosage , Retrospective Studies , Treatment OutcomeABSTRACT
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.
Subject(s)
Fragile X Syndrome/complications , Fragile X Syndrome/psychology , Schizophrenia/etiology , Schizophrenia/genetics , Age of Onset , Child , Comorbidity , Female , Genotype , Humans , PhenotypeABSTRACT
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.
Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Family , Membrane Glycoproteins/genetics , Membrane Transport Proteins/genetics , Nerve Tissue Proteins/genetics , Confidence Intervals , Databases, Factual , Dopamine Plasma Membrane Transport Proteins , Humans , Odds Ratio , Receptors, Dopamine D2/genetics , Receptors, Dopamine D4ABSTRACT
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.
Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Proteins/genetics , Receptors, Dopamine D4/genetics , Alleles , Attention Deficit Disorder with Hyperactivity/metabolism , Child , Dopamine Plasma Membrane Transport Proteins/genetics , Dopamine Plasma Membrane Transport Proteins/metabolism , Haplotypes , Humans , Norepinephrine/genetics , Norepinephrine/metabolism , Polymorphism, Genetic/genetics , Protein Transport/genetics , Proteins/metabolism , Receptors, Estrogen , Risk Factors , Serotonin/genetics , Serotonin/metabolismABSTRACT
The underlying neurobiology of autism, a severe pervasive developmental disorder, remains unknown. Few neocortical brain MRI abnormalities have been reported. Using rest functional brain imaging, two independent studies have described localized bilateral temporal hypoperfusion in children with primary autism. In order to search for convergent evidence of anatomical abnormalities in autistic children, we performed an anatomical MRI study using optimized whole-brain voxel-based morphometry (VBM). High-resolution 3-D T1-weighted MRI data sets were acquired in 21 children with primary autism (mean age 9.3 +/- 2.2 years) and 12 healthy control children (mean age 10.8 +/- 2.7 years). By comparing autistic children to normal children, we found bilaterally significant decreases of grey matter concentration located in superior temporal sulcus (STS) (P < 0.05 corrected, after small volume correction; SVC). Children with autism were also found to have a decrease of white matter concentration located in the right temporal pole and in cerebellum (P < 0.05, corrected) compared to normal children. These results suggest that autism is associated with bilateral anatomical abnormalities localized in the STS and are remarkably consistent with functional hypoperfusion previously reported in children with autism. The multimodal STS areas are involved in highest level of cortical integration of both sensory and limbic information. Moreover, the STS is now recognized as a key cortical area of the "social brain" and is implicated in social perceptual skills that are characteristically impaired in autism. Therefore, the convergent anatomical and functional temporal abnormalities observed in autism may be important in the understanding of brain behavior relationships in this severe developmental disorder.
Subject(s)
Autistic Disorder/pathology , Image Processing, Computer-Assisted , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Mathematical Computing , Temporal Lobe/abnormalities , Adolescent , Atrophy , Autistic Disorder/diagnosis , Child , Dominance, Cerebral/physiology , Female , Humans , Male , Reference Values , Social Perception , Software , Temporal Lobe/pathologyABSTRACT
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.
