In resting state functional magnetic resonance imaging (fMRI) studies of autism spectrum disorders (ASDs) decreased frontal-posterior functional connectivity is a persistent finding. However, the ...picture of the default mode network (DMN) hypoconnectivity remains incomplete. In addition, the functional connectivity analyses have been shown to be susceptible even to subtle motion. DMN hypoconnectivity in ASD has been specifically called for re-evaluation with stringent motion correction, which we aimed to conduct by so-called scrubbing. A rich set of default mode subnetworks can be obtained with high dimensional group independent component analysis (ICA) which can potentially provide more detailed view of the connectivity alterations. We compared the DMN connectivity in high-functioning adolescents with ASDs to typically developing controls using ICA dual-regression with decompositions from typical to high dimensionality. Dual-regression analysis within DMN subnetworks did not reveal alterations but connectivity between anterior and posterior DMN subnetworks was decreased in ASD. The results were very similar with and without motion scrubbing thus indicating the efficacy of the conventional motion correction methods combined with ICA dual-regression. Specific dissociation between DMN subnetworks was revealed on high ICA dimensionality, where networks centered at the medial prefrontal cortex and retrosplenial cortex showed weakened coupling in adolescents with ASDs compared to typically developing control participants. Generally the results speak for disruption in the anterior-posterior DMN interplay on the network level whereas local functional connectivity in DMN seems relatively unaltered.
The authors examined pregnancy and obstetric complications in association with autism spectrum disorders (ASD) in children of participants from the Nurses' Health Study II, a prospective national ...cohort with information collected through biennial mailed questionnaires since 1989. Logistic regression was used to obtain crude and adjusted odds ratios for ASD, and by diagnostic subgroup. Seven hundred and ninety-three cases were reported among 66,445 pregnancies. Pregnancy complications and obstetric suboptimality factors were assessed by maternal report of occurrence in first birth and, in secondary analyses, in any birth. Complications and a suboptimality score were significantly associated with having a child with ASD (OR 1.49, 95% CI 1.26, 1.77, P<0.0001 for pregnancy complications in first birth and 2.76, 95% CI 2.04, 3.74, P<0.0001 comparing individuals with four or more obstetric suboptimality factors in first birth to those with none; results similar when assessed in any birth). In particular, gestational diabetes was associated with a significantly increased risk of ASD in results of primary and sensitivity analyses (OR in primary analysis = 1.76, 95% CI 1.34, 2.32, P<0.0001); suboptimal parity and suboptimal age-at-first-birth were also individual factors associated with ASD. Associations were similar by diagnostic subgroup, suggesting autism, Asperger syndrome, and other Pervasive Developmental Disorders are all associated with pregnancy complications. Consistent with previous research, the general class of pregnancy complications was associated with ASD as a whole. Additional work will be required to more fully assess the role of gestational diabetes.
To identify heritable symptom-based subtypes of Tourette syndrome (TS).
Forty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). ...Item-level exploratory factor and latent class analyses (LCA) were used to identify tic-based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined.
A 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 × 10(-18)).
Expanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies.
Background Obsessive–compulsive disorder (OCD) has a broadly diverse clinical expression that may reflect etiologic heterogeneity. Several adult studies have identified consistent symptom dimensions ...of OCD. The purpose of this study was to conduct an exploratory principal components analysis of obsessive–compulsive (OC) symptoms in children and adolescents with OCD to identify improved phenotypes for future studies. Methods This study examined lifetime occurrence of OC symptoms included in the 13 symptom categories of the Yale–Brown Obsessive Compulsive Scale (Y-BOCS) and the Children’s Yale-Brown Obsessive–Compulsive Scale (CY-BOCS). Principal components analysis with promax rotation was performed on 231 children and adolescents with OCD and compared with results of similar adult studies. Results A four-factor solution emerged explaining 59.8% of symptom variance characterized by 1) symmetry/ordering/repeating/checking; 2) contamination/cleaning/aggressive/somatic; 3) hoarding; and 4) sexual/religious symptoms. All factors included core symptoms that have been consistently observed in adult studies of OCD. Conclusions In children and adolescents, OCD is a multidimensional disorder. Symptom dimensions are predominantly congruent with those described in similar studies of adults with OCD, suggesting fairly consistent covariation of OCD symptoms through the developmental course. Future work is required to understand changes in specific symptom dimensions observed across the life span.
Obsessive-compulsive disorder (OCD) is a common and debilitating psychiatric illness. Although a genetic component contributes to its etiology, no single gene or mechanism has been identified to the ...OCD susceptibility. The catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A) genes have been investigated in previous OCD studies, but the results are still unclear. More recently, Taylor (2013) in a comprehensive meta-analysis of genetic association studies has identified COMT and MAO-A polymorphisms involved with OCD. In an effort to clarify the role of these two genes in OCD vulnerability, a family-based association investigation was performed as an alternative strategy to the classical case-control design.
Transmission disequilibrium analyses were performed after genotyping 13 single-nucleotide polymorphisms (eight in COMT and five in MAO-A) in 783 OCD trios (probands and their parents). Four different OCD phenotypes (from narrow to broad OCD definitions) and a SNP x SNP epistasis were also analyzed.
OCD, broad and narrow phenotypes,were not associated with any of the investigated COMT and MAO-A polymorphisms. In addition, the analyses of gene-gene interaction did not show significant epistatic influences on phenotype between COMT and MAO-A.
The findings do not support an association between DSM-IV OCD and the variants of COMT or MAO-A. However, results from this study cannot exclude the contribution of these genes in the manifestation of OCD. The evaluation of broader spectrum phenotypes could help to understand the role of these and other genes in the pathophysiology of OCD and its spectrum disorders.
It is not known whether reproductive factors early in the mother’s life influence risk of autism spectrum disorders (ASD). We assessed maternal age at menarche, menstrual cycle characteristics during ...adolescence, oral contraceptive use prior to first birth, body shape, and body mass index (BMI) in association with ASD using binomial regression in a cohort study of 61,596 women, including 743 cases. Overall, early life factors were not associated with ASD, though early age at menarche (RR for age 10 or less = 1.54, 95% CI 1.18, 2.02,
p
= 0.0002) and BMI at age 18 of ≥30 (RR 2.03, 95% CI 1.34, 3.08,
p
= 0.0008) were significantly associated with increased risk of ASD. Further work should investigate the potential influence of these factors.
Background: An increasing number of women are utilizing fertility treatments, but little is known about their relation to autism spectrum disorders (ASD).
Methods: To determine the association ...between maternal fertility therapy use and risk of having a child with ASD, we conducted a nested case‐control study within the Nurses' Health Study II (n = 116,430). Maternally reported diagnoses of ASD were confirmed through a supplementary questionnaire and, in a subgroup, the Autism Diagnostic Interview‐Revised. Controls were randomly selected by frequency matching to case children's year of birth. Associations were examined by self‐reported infertility and type of therapy using conditional logistic regression.
Results: In all, 9% of the 507 cases and 7% of 2,529 controls indicated fertility therapy use for the index pregnancy. No significant associations with self‐reported fertility therapies or history of infertility were seen in primary analyses. In subgroup analyses of women with maternal age ≥35 years (n = 1,020), artificial insemination was significantly associated with ASD; ovulation inducing drug (OID) use was significantly associated in crude but not adjusted analyses (odds ratio 1.81, 95% CI 0.96–3.42). Results were similar by diagnostic subgroup, though within the advanced maternal age group, OID and artificial insemination were significantly associated with Asperger syndrome and pervasive developmental disorder not‐otherwise specified, but not autistic disorder.
Conculsion: Assisted reproductive therapy and history of infertility did not increase risk of having a child with ASD in this study. However, the associations observed with OID and artificial insemination among older mothers, for whom these exposures are more common, warrant further investigation.
Abstract Background Clinicians have long considered doubt to be a fundamental characteristic of obsessive–compulsive disorder (OCD). However, the clinical relevance of doubt in OCD has not been ...addressed. Methods Participants included 1182 adults with OCD who had participated in family and genetic studies of OCD. We used a clinical measure of the severity of doubt, categorized as none, mild, moderate, severe, or extreme. We evaluated the relationship between doubt and OCD clinical features, Axis I disorders, personality and personality disorder dimensions, impairment, and treatment response. Results The severity of doubt was inversely related to the age at onset of OCD symptoms. Doubt was strongly related to the number of checking symptoms and, to a lesser extent, to the numbers of contamination/cleaning and hoarding symptoms. Doubt also was related to the lifetime prevalence of recurrent major depression and generalized anxiety disorder; to the numbers of avoidant, dependent, and obsessive–compulsive personality disorder traits; and to neuroticism and introversion. Moreover, doubt was strongly associated with global impairment and poor response to cognitive behavioral treatment (CBT), even adjusting for OCD severity and other correlates of doubt. Conclusions Doubt is associated with important clinical features of OCD, including impairment and cognitive–behavioral treatment response.
Trichotillomania/hair pulling disorder (HPD) and excoriation/skin picking disorder (SPD) are childhood-onset, body-focused repetitive behaviors that are thought to share genetic susceptibility and ...underlying pathophysiology with obsessive–compulsive disorder (OCD) and Tourette syndrome (TS). We sought to determine the prevalence of
DSM
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5
HPD and SPD in TS patients, and to identify clinical factors most associated with their co-morbidity with TS. Participants included 811 TS patients recruited from TS specialty clinics for a multi-center genetic study. Patients were assessed using standardized, validated semi-structured interviews. HPD and SPD diagnoses were determined using a validated self-report questionnaire. HPD/SPD prevalence rates were calculated, and clinical predictors were evaluated using regression modeling. 3.8 and 13.0% of TS patients met
DSM
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5
criteria for HPD and SPD, respectively. In univariable analyses, female sex, OCD, and both tic and obsessive–compulsive symptom severity were among those associated with HPD and/or SPD. In multivariable analyses, only lifetime worst-ever motor tic severity remained significantly associated with HPD. Female sex, co-occurring OCD, ADHD, and motor tic severity remained independently associated with SPD. This is the first study to examine HPD and SPD prevalence in a TS sample using semi-structured diagnostic instruments. The prevalence of HPD and SPD in TS patients, and their association with increased tic severity and co-occurring OCD, suggests that clinicians should screen children with TS and related disorders for HPD/SPD, particularly in females and in those with co-occurring OCD. This study also helps set a foundation for subsequent research regarding HPD/SPD risk factors, pathophysiology, and treatment models.
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