Variations of the candidate SEZ6L2 gene on Chromosome 16p11.2 in patients with autism spectrum disorders and in human populations.

Background: Autism spectrum disorders (ASD) are a group of severe childhood neurodevelopmental disorders with still unknown etiology. One of the most frequently reported associations is the presence of recurrent de novo or inherited microdeletions and microduplications on chromosome 16p11.2.

Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population.

Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of the melatonin pathway has been reported in circadian disorders, diabetes and autism spectrum disorders (ASD). However, very little is known about the genetic variability of melatonin receptors in humans.

An investigation of ribosomal protein L10 gene in autism spectrum disorders.

Background: Autism spectrum disorders (ASD) are severe neurodevelopmental disorders with the male:female ratio of 4:1, implying the contribution of X chromosome genetic factors to the susceptibility of ASD. The ribosomal protein L10 (RPL10) gene, located on chromosome Xq28, codes for a key protein in assembling large ribosomal subunit and protein synthesis. Two non-synonymous mutations of RPL10, L206M and H213Q, were identified in four boys with ASD.

Polymorphisms of coding trinucleotide repeats of homeogenes in neurodevelopmental psychiatric disorders.

Objectives: Autism (MIM#209850) and schizophrenia (MIM#181500) are both neurodevelopmental psychiatric disorders characterized by a highly genetic component. Homeogenes and forkhead genes encode transcription factors, which have been involved in brain development and cell differentiation. Thus, they are relevant candidate genes for psychiatric disorders.

Analysis of X chromosome inactivation in autism spectrum disorders.

Autism spectrum disorders (ASD) are complex genetic disorders more frequently observed in males. Skewed X chromosome inactivation (XCI) is observed in heterozygous females carrying gene mutations involved in several X-linked syndromes. In this study, we aimed to estimate the role of X-linked genes in ASD susceptibility by ascertaining the XCI pattern in a sample of 543 informative mothers of children with ASD and in a sample of 163 affected girls.

Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.

SHANK3 (also known as ProSAP2) regulates the structural organization of dendritic spines and is a binding partner of neuroligins; genes encoding neuroligins are mutated in autism and Asperger syndrome. Here, we report that a mutation of a single copy of SHANK3 on chromosome 22q13 can result in language and/or social communication disorders. These mutations concern only a small number of individuals, but they shed light on one gene dosage-sensitive synaptic pathway that is involved in autism spectrum disorders.

Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder.

Background: Executive dysfunctions have been studied as a potential endophenotype associated with the genetic basis of autism. Given that recent findings from clinical and molecular genetic studies suggest that autism and obsessive-compulsive disorder (OCD) could share a common pattern of heritability, we assessed executive functions as a possible common cognitive endophenotype in unaffected family members of individuals with either autism or OCD.

Methods: Five tests assessing executive functions (Tower of London, verbal fluency, design fluency, trail making and association fluency) were proposed to 58 unaffected first-degree relatives (parents and siblings) of probands with autism and 64 unaffected first-degree relatives of OCD patients.

Exploratory analysis of obsessive compulsive symptom dimensions in children and adolescents: a prospective follow-up study.

Background: Recent statistical approaches based on factor analysis of obsessive compulsive (OC) symptoms in adult patients have identified dimensions that seem more effective in symptom-based taxonomies and appear to be more stable over time. Although a phenotypic continuum from childhood to adulthood has been hypothesized, no factor analytic studies have been performed in juvenile patients, and the stability of OC dimensions in children and adolescents has not been assessed.

Methods: This study was designed to perform an exploratory factor analysis of OC symptoms in a sample of children and adolescents with OC disorder (OCD) and to investigate the course of factors over time (mean follow-up period: four years).

Platelet serotonergic markers as endophenotypes for obsessive-compulsive disorder.

Although compelling evidence has shown that obsessive-compulsive disorder (OCD) has a strong genetic component, its genetic basis remains to be elucidated. Identifying biological abnormalities in nonaffected relatives is one of the strategies advocated to isolate genetic vulnerability factors in complex disorders. Since peripheral serotonergic disturbances are frequently observed in OCD patients, the aim of this study was to investigate if they could represent endophenotypes, by searching for similar abnormalities in the unaffected parents of OCD patients.

Admixture analysis of age at onset in obsessive-compulsive disorder.

Background: Age at onset (AAO) has been useful to explore the clinical, neurobiological and genetic heterogeneity of obsessive-compulsive disorder (OCD). However, none of the various thresholds of AAO used in previous studies have been validated, and it remains an unproven notion that AAO is a marker for different subtypes of OCD. If AAO is a clinical indicator of different biological subtypes, then subgroups based on distinct AAOs should have separate normal distributions as well as different clinical characteristics.

Perception of complex sounds in autism: abnormal auditory cortical processing in children.

Objective: The authors have previously described less activation of left speech-related temporal areas in adults with autism when listening to speech-like sounds than in normal adults. Here, they investigated whether this abnormal cortical processing was also present in children with primary autism.

Method: Regional cerebral blood flow was measured with positron emission tomography after premedication in 11 autistic children and six nonautistic mentally retarded children during rest and while they were listening to speech-like sounds.

Discrimination of face identities and expressions in children with autism: same or different?

Autism is a pervasive developmental disorder (PDD) characterized by the association of communication and socialization impairments, and by repetitive stereotyped behaviours. The Minnesota Test of Affective Processing (MNTAP) was used to investigate the discrimination of face identities and face expressions by autistic children. Young children in the 6- to 10-year-old age range suffering from PDD were compared to paired normal children.

Mental disorders in obese children and adolescents.

Objective: To evaluate the type and frequency of psychiatric disorders in obese children and adolescents; to assess the correlation between psychopathology and severity of obesity; to explore the relationship between psychiatric disorders in obese children and obesity and psychopathology in their parents.

Methods: One hundred fifty-five children referred and followed for obesity were evaluated (98 girls and 57 boys; age, 5 to 17 years). Psychiatric disorders were assessed through a standardized diagnostic interview schedule (K-SADS R) and self-report questionnaires completed by the child (STAIC Trait-anxiety and CDI for depression) or his (her) parents (CBCL or GHQ).

Frequency and transmission of glutamate receptors GRIK2 and GRIK3 polymorphisms in patients with obsessive compulsive disorder.

Several lines of evidence suggest that obsessive compulsive disorder (OCD) could be the consequence of glutamatergic dysfunction. We performed a case-control study in 156 patients and 141 controls and the transmission disequilibrium test in 124 parent-offspring trios to search for association between OCD and two kainate receptors, GRIK2 and GRIK3. Using three single nucleotide polymorphisms (SNP) in GRIK2 and one in GRIK3, we found no evidence for association in case-control or family-based analyses.

Platelet serotonergic predictors of clinical improvement in obsessive compulsive disorder.

Objective: Serotonin reuptake inhibitors (SRIs) are the most efficient pharmacological treatment of obsessive-compulsive disorders (OCD). Previous studies have suggested that some peripheral serotonergic parameters can be used to predict the clinical outcome of the treatment of OCD patients with SRIs. We tried to identify further peripheral serotonergic parameters that could help predict the clinical outcome of SRI treatment in a sample of patients with OCD.

Perception of complex sounds: abnormal pattern of cortical activation in autism.

Objective: Bilateral temporal hypoperfusion at rest was recently described in autism. In normal adults, these regions are activated by listening to speech-like sounds. To investigate auditory cortical processing in autism, the authors performed a positron emission tomography activation study.

Binge eating and psychopathology in severely obese adolescents.

Objective: The authors describe binge eating and psychopathology in severely obese adolescents who are seeking treatment for obesity and search for specific psychological features that may be associated with binge eating.

Method: Obese adolescents (n = 102) were assessed with the Binge Eating Scale (BES), the State-Trait Anxiety Inventory for Children (STAIC), the Beck Depression Inventory (BDI), Coopersmith's Self-Esteem Inventory (SEI), and the Body-Esteem subscale from the Piers-Harris Children's Self-Concept Scale (PHCSS). They were also evaluated with the Montgomery and Asberg Depression Rating Scale (MADRS) and the Brief Scale for Anxiety (BSA).

Psychopathology and quality of life for adolescents with asthma and their parents.

Asthma is known to have a direct impact on the quality of life of children with asthma and their families as a consequence of the attacks on day-to-day life. Psychopathological factors may be associated with poor quality of life by modulating the handicap and the patient's experience of it. The authors' objective was to evaluate the relationship between emotional and behavioral problems and quality of life, as assessed by the Pediatric Asthma Quality of Life Questionnaire and the Pediatric Asthma Caregiver's Quality of Life Questionnaire.

Association between the dopamine receptor D4 (DRD4) gene and obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a frequent and disabling anxiety disorder. Dopamine (DA) might be involved in its pathophysiology, therefore DA receptors are candidate genes in OCD. A 48-base pairs (bp) polymorphism located in the third exon of the dopamine receptor type 4 (DRD4) gene has been described.

Fringe phenotypes in autism: a review of clinical, biochemical and cognitive studies.

Progress in identifying the genetic vulnerability factors in autism requires correct identification of the inherited phenotype(s). This can be achieved not only by the accurate description of the affected subject but also by the identification of vulnerability traits in non-affected relatives of autistic probands. This review will focus on this last strategy and principally on clinical, biochemical and cognitive traits.