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Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay.

April 16, 2014 - 8:49am

Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay.

Pediatrics. 2014 Apr 14;

Authors: Harrington RA, Lee LC, Crum RM, Zimmerman AW, Hertz-Picciotto I

Abstract
OBJECTIVE: To examine associations between prenatal use of selective serotonin reuptake inhibitors (SSRIs) and the odds of autism spectrum disorders (ASDs) and other developmental delays (DDs).
METHODS: A total of 966 mother-child pairs were evaluated (492 ASD, 154 DD, 320 typical development [TD]) from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based case-control study. Standardized measures confirmed developmental status. Interviews with biological mothers ascertained prenatal SSRI use, maternal mental health history, and sociodemographic information.
RESULTS: Overall, prevalence of prenatal SSRI exposure was lowest in TD children (3.4%) but did not differ significantly from ASD (5.9%) or DD (5.2%) children. Among boys, prenatal SSRI exposure was nearly 3 times as likely in children with ASD relative to TD (adjusted odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.07-7.93); the strongest association occurred with first-trimester exposure (OR: 3.22; 95% CI: 1.17-8.84). Exposure was also elevated among boys with DD (OR: 3.39; 95% CI: 0.98-11.75) and was strongest in the third trimester (OR: 4.98; 95% CI: 1.20-20.62). Findings were similar among mothers with an anxiety or mood disorder history.
CONCLUSIONS: In boys, prenatal exposure to SSRIs may increase susceptibility to ASD or DD. Findings from published studies on SSRIs and ASD continues to be inconsistent. Potential recall bias and residual confounding by indication are concerns. Larger samples are needed to replicate DD results. Because maternal depression itself carries risks for the fetus, the benefits of prenatal SSRI use should be carefully weighed against potential harms.

PMID: 24733881 [PubMed - as supplied by publisher]

Stress and well-being among parents of children with Potocki-Lupski syndrome.

April 16, 2014 - 8:49am
Related Articles

Stress and well-being among parents of children with Potocki-Lupski syndrome.

J Genet Couns. 2013 Oct;22(5):633-42

Authors: Carter RD, Raia M, Ewing-Cobbs L, Gambello M, Hashmi SS, Peterson SK, Robbins-Furman P, Potocki L

Abstract
Potocki-Lupski syndrome (PTLS) or duplication 17p11.2 syndrome is a newly characterized condition causing a variety of health problems with variable severity, including failure to thrive in infancy and childhood, hypotonia, structural heart anomalies, cognitive impairments, speech and learning difficulties, and autism. Due to its recent clinical characterization little is known about the psychosocial impact of this condition on patients and their families. This study evaluated whether parental psychosocial outcomes were associated with children's PTLS disease severity. Parents of 58 children with PTLS completed a cross-sectional survey that assessed parental stress, quality of life, and coping skills. Parental functioning was associated with greater severity of feeding difficulty and with lower severity of a cardiovascular defect. Findings from this study highlight potential support needs of parents of children affected by PTLS and suggest ways in which these needs may be addressed.

PMID: 23709095 [PubMed - indexed for MEDLINE]

Does a duty of disclosure foster special treatment of genetic research participants?

April 16, 2014 - 8:49am
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Does a duty of disclosure foster special treatment of genetic research participants?

J Genet Couns. 2013 Oct;22(5):654-61

Authors: Hayeems RZ, Miller FA, Bytautas JP, Li L

Abstract
The principle that research participants not receive enhanced care compared to non-participants may be challenged by a duty to disclose genetic research results, especially where care is otherwise inaccessible. Autism researchers' attitudes toward providing enhanced care to study participants were analyzed quantitatively using descriptive and multivariate analyses of survey data and qualitatively through thematic analysis of interview data. Approximately half of survey respondents (n = 168, RR = 44 %) agreed they should provide additional knowledge (52 %) or services (48 %) to study participants that may not be available to non-participants. Qualitatively (n = 23), respondents were motivated by the notion of reciprocity but highlighted tensions when research enables access to expertise and therapeutic resources that are otherwise difficult to obtain. For researchers, feeling obliged to report research results may be in conflict with the obligation to avoid special treatment of research participants; this may in turn threaten principles of voluntariness, autonomy, and justice.

PMID: 23681280 [PubMed - indexed for MEDLINE]

Social memory, amnesia, and autism: brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38.

April 16, 2014 - 8:49am
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Social memory, amnesia, and autism: brain oxytocin secretion is regulated by NAD+ metabolites and single nucleotide polymorphisms of CD38.

Neurochem Int. 2012 Nov;61(6):828-38

Authors: Higashida H, Yokoyama S, Huang JJ, Liu L, Ma WJ, Akther S, Higashida C, Kikuchi M, Minabe Y, Munesue T

Abstract
Previously, we demonstrated that CD38, a transmembrane protein with ADP-ribosyl cyclase activity, plays a critical role in mouse social behavior by regulating the release of oxytocin (OXT), which is essential for mutual recognition. When CD38 was disrupted, social amnesia was observed in Cd38 knockout mice. The autism spectrum disorders (ASDs), characterized by defects in reciprocal social interaction and communication, occur either sporadically or in a familial pattern. However, the etiology of ASDs remains largely unknown. Therefore, the theoretical basis for pharmacological treatments has not been established. Hence, there is a rationale for investigating single nucleotide polymorphisms (SNPs) in the human CD38 gene in ASD subjects. We found several SNPs in this gene. The SNP rs3796863 (C>A) was associated with high-functioning autism (HFA) in American samples from the Autism Gene Resource Exchange. Although this finding was partially confirmed in low-functioning autism subjects in Israel, it has not been replicated in Japanese HFA subjects. The second SNP of interest, rs1800561 (4693C>T), leads to the substitution of an arginine (R) at codon 140 by tryptophan (W; R140W) in CD38. This mutation was found in four probands of ASD and in family members of three pedigrees with variable levels of ASD or ASD traits. The plasma levels of OXT in ASD subjects with the R140W allele were lower than those in ASD subjects lacking this allele. The OXT levels were unchanged in healthy subjects with or without this mutation. One proband with the R140W allele receiving intranasal OXT for approximately 3years showed improvement in areas of social approach, eye contact and communication behaviors, emotion, irritability, and aggression. Five other ASD subjects with mental deficits received nasal OXT for various periods; three subjects showed improved symptoms, while two showed little or no effect. These results suggest that SNPs in CD38 may be possible risk factors for ASD by abrogating OXT function and that some ASD subjects can be treated with OXT in preliminary clinical trials.

PMID: 22366648 [PubMed - indexed for MEDLINE]

Focusing on Cause or Cure?: Priorities and Stakeholder Presence in Childhood Psychiatry Research.

April 15, 2014 - 8:26am

Focusing on Cause or Cure?: Priorities and Stakeholder Presence in Childhood Psychiatry Research.

AJOB Prim Res. 2014 Jan 1;5(1):44-55

Authors: Milner LC, Cho MK

Abstract
BACKGROUND: Biomedical research is influenced by many factors, including the involvement of stakeholder groups invested in research outcomes. Stakeholder involvement in research efforts raise questions of justice as their specific interests and motivations play a role in directing research resources that ultimately produce knowledge shaping how different conditions (and affected individuals) are understood and treated by society. This issue is highly relevant to child psychiatry research where diagnostic criteria and treatment strategies are often controversial. Biological similarities and stakeholder differences between attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) provide an opportunity to explore this issue by comparing research foci and stakeholder involvement in these conditions.
METHODS: A subset of ADHD and ASD research articles published between 1970-2010 were randomly selected from the PubMed database and coded for research focus, funding source(s), and author-reported conflicts of interest (COIs). Chi-square analyses were performed to identify differences between and within ADHD and ASD research across time.
RESULTS: The proportion of ADHD research dedicated to basic, description, and treatment research was roughly similar and remained stable over time, while ASD research showed a significant increase in basic research over the past decade. Government was the primary research funder for both conditions, but for-profit funders were a notable presence in ADHD research, while joint-funding efforts between non-profit and government funders were a notable presence in ASD research. Lastly, COIs were noted more frequently in ADHD than in ASD research.
CONCLUSIONS: Our study shows significant differences in research foci and funding sources between the conditions, and identifies the specific involvement of for-profit and non-profit groups in ADHD and ASD, respectively. Our findings highlight the relationship between stakeholders outside the research community and research trajectories and suggest that examinations of these relationships must be included in broader considerations of biomedical research ethics.

PMID: 24729931 [PubMed - as supplied by publisher]

Correction: DUF1220 Dosage Is Linearly Associated with Increasing Severity of the Three Primary Symptoms of Autism.

April 15, 2014 - 8:26am

Correction: DUF1220 Dosage Is Linearly Associated with Increasing Severity of the Three Primary Symptoms of Autism.

PLoS Genet. 2014 Apr;10(4):e1004373

Authors: The PLOS Genetics Staff

Abstract
[This corrects the article DOI: 10.1371/journal.pgen.1004241.].

PMID: 24728508 [PubMed - as supplied by publisher]

Variable phenotype in 17q12 microdeletions: clinical and molecular characterization of a new case.

April 15, 2014 - 8:26am
Related Articles

Variable phenotype in 17q12 microdeletions: clinical and molecular characterization of a new case.

Gene. 2014 Apr 1;538(2):373-8

Authors: Palumbo P, Antona V, Palumbo O, Piccione M, Nardello R, Fontana A, Carella M, Corsello G

Abstract
Microdeletions of 17q12 including the hepatocyte nuclear factor 1 beta (HNF1B) gene, as well as point mutations of this gene, are associated with the Renal Cysts and Diabetes syndrome (RCAD, OMIM 137920) and genitourinary alterations. Also, microdeletions encompassing HNF1B were identified as a cause of Mayer-Rokitansky-Küster-Hauser Syndrome (MRKH, OMIM 277000) in females and, recently, were associated with intellectual disability, autistic features, cerebral anomaly and facial dysmorphisms. In this report, we describe a boy with a deletion in 17q12 region detected by SNP array, encompassing the HNF1B gene, that showed dysmorphic features, intellectual disability (ID), serious speech delay and autistic features. In addition, obesity was observed. In order to study the parental origin of the rearrangement, we analyzed selected SNPs in the deleted area in the patient and his parents, showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of maternal origin. Our case confirms the incomplete penetrance and variable expressivity of this deletion, its complex clinical variability, and strengthens the evidence that ID and stereotyped behaviors may be part of the phenotypic spectrum characterizing the affected patients. Also, it is useful to further delineate the phenotypes associated to the deletion being the first case in which obesity has been documented. We present a genotype-phenotype correlation discussing the possible role of some genes, encompassed by the deletion, in the etiology of the observed phenotypes.

PMID: 24487052 [PubMed - indexed for MEDLINE]

Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.

April 15, 2014 - 8:26am
Related Articles

Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.

Nutrition. 2013 Oct;29(10):1175-85

Authors: Das UN

Abstract
Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission, and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, γ-aminobutyric acid, and catecholamines and cytokines are altered. Antioxidants, vitamins, minerals, and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids, and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of PUFAs and their metabolites resulting in excess production of proinflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Based on these evidences, it is proposed that selective delivery of BDNF and methods designed to augment the production of anti-inflammatory cytokines and eicosanoids and PUFAs may prevent, arrest, or reverse the autism disease process.

PMID: 23911220 [PubMed - indexed for MEDLINE]

Focusing on Cause or Cure?: Priorities and Stakeholder Presence in Childhood Psychiatry Research.

April 15, 2014 - 8:26am

Focusing on Cause or Cure?: Priorities and Stakeholder Presence in Childhood Psychiatry Research.

AJOB Prim Res. 2014 Jan 1;5(1):44-55

Authors: Milner LC, Cho MK

Abstract
BACKGROUND: Biomedical research is influenced by many factors, including the involvement of stakeholder groups invested in research outcomes. Stakeholder involvement in research efforts raise questions of justice as their specific interests and motivations play a role in directing research resources that ultimately produce knowledge shaping how different conditions (and affected individuals) are understood and treated by society. This issue is highly relevant to child psychiatry research where diagnostic criteria and treatment strategies are often controversial. Biological similarities and stakeholder differences between attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) provide an opportunity to explore this issue by comparing research foci and stakeholder involvement in these conditions.
METHODS: A subset of ADHD and ASD research articles published between 1970-2010 were randomly selected from the PubMed database and coded for research focus, funding source(s), and author-reported conflicts of interest (COIs). Chi-square analyses were performed to identify differences between and within ADHD and ASD research across time.
RESULTS: The proportion of ADHD research dedicated to basic, description, and treatment research was roughly similar and remained stable over time, while ASD research showed a significant increase in basic research over the past decade. Government was the primary research funder for both conditions, but for-profit funders were a notable presence in ADHD research, while joint-funding efforts between non-profit and government funders were a notable presence in ASD research. Lastly, COIs were noted more frequently in ADHD than in ASD research.
CONCLUSIONS: Our study shows significant differences in research foci and funding sources between the conditions, and identifies the specific involvement of for-profit and non-profit groups in ADHD and ASD, respectively. Our findings highlight the relationship between stakeholders outside the research community and research trajectories and suggest that examinations of these relationships must be included in broader considerations of biomedical research ethics.

PMID: 24729931 [PubMed - as supplied by publisher]

Correction: DUF1220 Dosage Is Linearly Associated with Increasing Severity of the Three Primary Symptoms of Autism.

April 15, 2014 - 8:26am

Correction: DUF1220 Dosage Is Linearly Associated with Increasing Severity of the Three Primary Symptoms of Autism.

PLoS Genet. 2014 Apr;10(4):e1004373

Authors: The PLOS Genetics Staff

Abstract
[This corrects the article DOI: 10.1371/journal.pgen.1004241.].

PMID: 24728508 [PubMed - as supplied by publisher]

Variable phenotype in 17q12 microdeletions: clinical and molecular characterization of a new case.

April 15, 2014 - 8:26am
Related Articles

Variable phenotype in 17q12 microdeletions: clinical and molecular characterization of a new case.

Gene. 2014 Apr 1;538(2):373-8

Authors: Palumbo P, Antona V, Palumbo O, Piccione M, Nardello R, Fontana A, Carella M, Corsello G

Abstract
Microdeletions of 17q12 including the hepatocyte nuclear factor 1 beta (HNF1B) gene, as well as point mutations of this gene, are associated with the Renal Cysts and Diabetes syndrome (RCAD, OMIM 137920) and genitourinary alterations. Also, microdeletions encompassing HNF1B were identified as a cause of Mayer-Rokitansky-Küster-Hauser Syndrome (MRKH, OMIM 277000) in females and, recently, were associated with intellectual disability, autistic features, cerebral anomaly and facial dysmorphisms. In this report, we describe a boy with a deletion in 17q12 region detected by SNP array, encompassing the HNF1B gene, that showed dysmorphic features, intellectual disability (ID), serious speech delay and autistic features. In addition, obesity was observed. In order to study the parental origin of the rearrangement, we analyzed selected SNPs in the deleted area in the patient and his parents, showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of maternal origin. Our case confirms the incomplete penetrance and variable expressivity of this deletion, its complex clinical variability, and strengthens the evidence that ID and stereotyped behaviors may be part of the phenotypic spectrum characterizing the affected patients. Also, it is useful to further delineate the phenotypes associated to the deletion being the first case in which obesity has been documented. We present a genotype-phenotype correlation discussing the possible role of some genes, encompassed by the deletion, in the etiology of the observed phenotypes.

PMID: 24487052 [PubMed - indexed for MEDLINE]

Autism, an overwhelming condition: history, etiopathogenesis, types, diagnosis, therapy and prognosis.

April 12, 2014 - 6:51am
Related Articles

Autism, an overwhelming condition: history, etiopathogenesis, types, diagnosis, therapy and prognosis.

Rev Med Chir Soc Med Nat Iasi. 2013 Jul-Sep;117(3):654-61

Authors: Amihăesei IC, Stefanachi E

Abstract
Autism is defined as a neurologic developmental disorder affecting brain and behavior, becoming usually apparent before 3 years of age, with stable evolution and no remission. No neurologic morphologic abnormality was associated with the disease. Several types of disease being described, autism is part of a larger spectrum known as autism spectrum disorders (ASD), or pervasive developmental disorders (PDD). The disease was first described long before it was defined and it has received its modern name. Main cause in the development of autism is considered to be genetic, up to 90 %. However, environmental factors could be incriminated, sometimes. The five types included in ASD are: Asperger syndrome, pervasive developmental disorder-not otherwise specified (PDD-NOS), typical autism, Rett syndrome and childhood disintegrative disorder (CDD). The classical triad of symptoms includes: social interaction impairments, communication impairments and repetitive, stereotype behavior. Diagnosis is based on interview of the parents and specialized observation of the suspected children. Main tools used in therapy are the family and the educational system. Well established, specialized programs of therapy were developed in time. Prognosis of autism is severe, since no cure is possible; nevertheless spontaneous recoveries do occur, in some cases.

PMID: 24502031 [PubMed - indexed for MEDLINE]

The interstitial duplication 15q11.2-q13 syndrome includes autism, mild facial anomalies and a characteristic EEG signature.

April 12, 2014 - 6:51am
Related Articles

The interstitial duplication 15q11.2-q13 syndrome includes autism, mild facial anomalies and a characteristic EEG signature.

Autism Res. 2013 Aug;6(4):268-79

Authors: Urraca N, Cleary J, Brewer V, Pivnick EK, McVicar K, Thibert RL, Schanen NC, Esmer C, Lamport D, Reiter LT

Abstract
Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism-associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2-q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum.

PMID: 23495136 [PubMed - indexed for MEDLINE]

The broad autism phenotype questionnaire: prevalence and diagnostic classification.

April 12, 2014 - 6:51am
Related Articles

The broad autism phenotype questionnaire: prevalence and diagnostic classification.

Autism Res. 2013 Apr;6(2):134-43

Authors: Sasson NJ, Lam KS, Childress D, Parlier M, Daniels JL, Piven J

Abstract
The Broad Autism Phenotype Questionnaire (BAPQ) was administered to a large community-based sample of biological parents of children with autism (PCAs) and comparison parents (CPs) (n = 1,692). Exploratory factor analysis and internal consistency parameters confirmed a robust three-factor structure of the BAPQ, corresponding to the proposed aloof, pragmatic language and rigidity subscales. Based upon the distribution of Broad Autism Phenotype (BAP) features in the general population, new normative cutoff values for BAPQ subscales were established that provide increased specificity relative to those previously reported, and thus enhance the utility of the BAPQ for diagnostically classifying the BAP. These cutoffs were also used to estimate prevalence of the BAP and its three components, with rates ranging between 14-23% for PCAs and between 5-9% for CPs. Analysis of patterns of BAP characteristics within family members revealed that BAP features were more likely to co-occur in PCAs relative to CPs. Collectively, these findings extend the utility of the BAPQ and provide additional evidence that it is an efficient and reliable tool for disaggregating the heterogeneity of autism through the identification of meaningful subgroups of parents. Autism Res 2013, 6: 134-143. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

PMID: 23427091 [PubMed - indexed for MEDLINE]

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