Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviours that are experienced as unwanted. Family and twin studies have demonstrated that OCD is a multifactorial ...familial condition that involves both polygenic and environmental risk factors. Neuroimaging studies have implicated the cortico-striato-thalamo-cortical circuit in the pathophysiology of the disorder, which is supported by the observation of specific neuropsychological impairments in patients with OCD, mainly in executive functions. Genetic studies indicate that genes affecting the serotonergic, dopaminergic and glutamatergic systems, and the interaction between them, play a crucial part in the functioning of this circuit. Environmental factors such as adverse perinatal events, psychological trauma and neurological trauma may modify the expression of risk genes and, hence, trigger the manifestation of obsessive-compulsive behaviours.
Attention deficit hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric disorder. In the present study, the authors investigated the presence of genomic convergence in the top findings ...of the five published genome-wide association studies (GWASs) of ADHD.
The authors carried out bioinformatics pathway analyses, using the Ingenuity and BiNGO tools, as well as a systematic literature analysis of 85 genes from the five published GWASs containing single nucleotide polymorphisms associated with ADHD at a p value <0.0001.
Findings revealed that 45 of the 85 top-ranked ADHD candidate genes encode proteins that fit into a neurodevelopmental network involved in directed neurite outgrowth. Data on copy number variations in patients with ADHD and data from animal studies provide further support for the involvement of this network in ADHD etiology. Several network proteins are also directly modulated by stimulants, the most commonly used psychopharmacological treatment for ADHD.
The authors have identified a protein network for ADHD that contributes to our understanding of the molecular basis of the disorder. In addition, the data suggest new candidate genes for ADHD and provide clues to future research into psychopharmacological ADHD treatments.
Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively ...few participants (<200), and none has examined the ages of highest risk for each TS-associated comorbidity or their etiologic relationship to TS.
To characterize the lifetime prevalence, clinical associations, ages of highest risk, and etiology of psychiatric comorbidity among individuals with TS.
Cross-sectional structured diagnostic interviews conducted between April 1, 1992, and December 31, 2008, of participants with TS (n = 1374) and TS-unaffected family members (n = 1142).
Lifetime prevalence of comorbid DSM-IV-TR disorders, their heritabilities, ages of maximal risk, and associations with symptom severity, age at onset, and parental psychiatric history.
The lifetime prevalence of any psychiatric comorbidity among individuals with TS was 85.7%; 57.7% of the population had 2 or more psychiatric disorders. The mean (SD) number of lifetime comorbid diagnoses was 2.1 (1.6); the mean number was 0.9 (1.3) when obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) were excluded, and 72.1% of the individuals met the criteria for OCD or ADHD. Other disorders, including mood, anxiety, and disruptive behavior, each occurred in approximately 30% of the participants. The age of greatest risk for the onset of most comorbid psychiatric disorders was between 4 and 10 years, with the exception of eating and substance use disorders, which began in adolescence (interquartile range, 15-19 years for both). Tourette syndrome was associated with increased risk of anxiety (odds ratio OR, 1.4; 95% CI, 1.0-1.9; P = .04) and decreased risk of substance use disorders (OR, 0.6; 95% CI, 0.3-0.9; P = .02) independent from comorbid OCD and ADHD; however, high rates of mood disorders among participants with TS (29.8%) may be accounted for by comorbid OCD (OR, 3.7; 95% CI, 2.9-4.8; P < .001). Parental history of ADHD was associated with a higher burden of non-OCD, non-ADHD comorbid psychiatric disorders (OR, 1.86; 95% CI, 1.32-2.61; P < .001). Genetic correlations between TS and mood (RhoG, 0.47), anxiety (RhoG, 0.35), and disruptive behavior disorders (RhoG, 0.48), may be accounted for by ADHD and, for mood disorders, by OCD.
This study is, to our knowledge, the most comprehensive of its kind. It confirms the belief that psychiatric comorbidities are common among individuals with TS, demonstrates that most comorbidities begin early in life, and indicates that certain comorbidities may be mediated by the presence of comorbid OCD or ADHD. In addition, genetic analyses suggest that some comorbidities may be more biologically related to OCD and/or ADHD rather than to TS.
Obsessive compulsive disorder (OCD) is a common psychiatric disorder that can have disabling effects on both adults and children. Twin, family, segregation, and linkage studies have demonstrated that ...OCD is familial, that the familiality is due in part to genetic factors and there are regions of the genome which very likely harbor susceptibility loci for OCD. Over 60 candidate gene studies have been conducted. Most studies have focused on genes in the serotonergic and dopaminergic pathways. Unfortunately, none have achieved genome-wide significance and with the exception of the glutamate transporter gene, none have been reliably replicated. Future research will requite much larger samples and the collaboration of researchers to be able to identify susceptibility loci for OCD.
Familial aspects of pediatric obsessive-compulsive disorder (OCD), including accommodation and treatment, have received notable and warranted attention. However, individual perspectives of its ...repercussions on family functioning, including emotional and occupational parental burden, have not been closely examined. The present study details this topic using a large multicenter sample.
Participants included 354 youth affected with OCD and their mothers and fathers ascertained through OCD programs in Boston, Massachusetts (n = 180) and Vancouver, British Columbia (n = 174). The validated OCD Family Functioning Scale and standard OCD measurements were completed. Descriptive, between-site, and cross-perspective comparative analyses were followed by regression model testing to predict family impairment.
Family functioning was negatively affected from youth, mother, and father perspectives. Impairment was reportedly more extensive at the time of worst OCD severity and was greater from maternal versus paternal viewpoints. Most frequently affected family tasks and implicated OCD symptoms included morning and bedtime routines and intrusive thoughts. Emotional repercussions in all members included stress and anxiety, followed by frustration or anger in youth and sadness in parents. Nearly half of mothers and one third of fathers reported daily occupational impairment. Compared with youth self-report, parents perceived fewer social and academic effects on their child. Family accommodation most consistently predicted family impairment, especially from parent perspectives. OCD and compulsion severity, contamination and religious obsessions, and comorbidities also predicted various perspectives of family subdomain impairment.
This study quantitatively details the pervasive burden that pediatric OCD places on families, as reported from complementary relative perspectives. Further attention to this topic is warranted in clinical and research realms.
The genetics of Tourette syndrome: A review O'Rourke, Julia A; Scharf, Jeremiah M; Yu, Dongmei ...
Journal of psychosomatic research,
12/2009, Letnik:
67, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Abstract Objectives This article summarizes and evaluates recent advances in the genetics of Gilles de la Tourette syndrome (GTS). Methods This is a review of recent literature focusing on (1) the ...genetic etiology of GTS; (2) common genetic components of GTS, attention deficit hyperactivity disorder (ADHD), and obsessive compulsive disorder (OCD); (3) recent linkage studies of GTS; (4) chromosomal translocations in GTS; and (5) candidate gene studies. Results Family, twin, and segregation studies provide strong evidence for the genetic nature of GTS. GTS is a heterogeneous disorder with complex inheritance patterns and phenotypic manifestations. Family studies of GTS and OCD indicate that an early-onset form of OCD is likely to share common genetic factors with GTS. While there apparently is an etiological relationship between GTS and ADHD, it appears that the common form of ADHD does not share genetic factors with GTS. The largest genome wide linkage study to date observed evidence for linkage on chromosome 2p23.2 ( P =3.8×10−5 ). No causative candidate genes have been identified, and recent studies suggest that the newly identified candidate gene SLITRK1 is not a significant risk gene for the majority of individuals with GTS. Conclusion The genetics of GTS are complex and not well understood. The Genome Wide Association Study (GWAS) design can hopefully overcome the limitations of linkage and candidate gene studies. However, large-scale collaborations are needed to provide enough power to utilize the GWAS design for discovery of causative mutations. Knowledge of susceptibility mutations and biological pathways involved should eventually lead to new treatment paradigms for GTS.
Doped polycrystalline silicon (poly-Si), when coupled with a thin SiO2 interlayer, is of large interest for crystalline silicon (c-Si) solar cells due to its outstanding passivating contact ...properties. To reach high levels of surface passivation, it is pivotal to hydrogenate the poly-Si and the underlying c-Si/SiO2 interface. This can be done by capping the poly-Si with a hydrogen-containing dielectric layer such as Al2O3 or SiNx, followed by a thermal anneal. On the basis of recent research, this work addresses several aspects of such hydrogenation by dielectric materials, including the effect of the annealing ambient, the thermal stability and reversibility of hydrogenation, the poly-Si doping level and c-Si surface texture. Additionally, the implementation of hydrogenation of poly-Si by dielectric materials in solar cells is discussed.
•Hydrogenation of poly-Si by dielectric materials improves the chemical surface passivation.•Al2O3 and SiNx dielectric capping layers strongly improve the thermal stability of poly-Si passivating contacts.•Dielectric capping layers of poly-Si passivating contacts can be used as sacrificial hydrogenation source.•The hydrogenation of poly-Si passivating contacts is completely reversible.•Hydrogenation by dielectrics is beneficial for surface passivation for all poly-Si doping levels.
Front/back poly-Si/SiO2 contact devices suffer from low short-circuit current density, Jsc, due to parasitic optical absorption in the front poly-Si layer. Thin poly-Si (~20 nm) allows for high Jsc ...but is not compatible with screen-printed fire-through contacts. We therefore study the effects of post-deposition etching of a thick poly-Si (200 nm) front layer by reactive ion etching (RIE) using the metal grid lines as a self-aligned mask. We show that passivation is maintained in the device during RIE and that Jsc is increased by a gain in the blue quantum efficiency response. However, our specific etching parameters cause non-uniform etching of the poly-Si leading to premature loss of passivation without optimal gain in Jsc. Etched, unpassivated layers can be re-passivated with a H-containing dielectric layer leading to a gain in Jsc, open circuit voltage,Voc, Fill-Factor, FF, and efficiency.
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•Reactive Ion Etching of poly-Si/SiO2 contacts on silicon solar cells thins poly-Si while preserving passivation.•Metal grid lines function as RIE masks to preserve poly-Si during RIE.•Selective area etching allows thick poly-Si under metal grid lines and thin poly-Si elsewhere, increasing Jsc.•Under certain RIE conditions passivation is lost before the entire poly-Si layer is removed.•Passivation can be restored with a post-RIE dielectric layer deposition and anneal.
Abstract Background Longitudinal research of well Amish children over 16 years to identify the pattern and frequency of prodromal symptoms/behaviors associated with onset of BPI disorder during ...childhood or adolescence. Methods: Parental informants were interviewed annually using structured and semi-structured interviews to record medical, developmental and behavioral/symptomatic data for their children in two samples. The bipolar sample had 115 children with a BPI parent. The control sample had 106 children of well parents, with and without a positive family history for mood disorders. A panel of clinicians assigned risk ratings independently and blind to family relations. Results: Eight children, age 13 or older, onset with BPI in the bipolar sample compared with one in the control sub-sample (well parent of a BPI sibling). The specific “pre-school” behaviors/symptoms that most identified children with BPI from well children in control samples were: sensitivity, crying, hyper-alertness, anxiety/worry and somatic complaints. During school years, parents reported mood (sad) and energy changes (low not high) decreased sleep and fearfulness as key symptoms. Limitations: The sample of 9 BPI onsets is small. However, a variable age of onset means many children remain at risk. Although not statistically significant, 34.6% of the bipolar sample youngsters carry risk ratings compared to 15.2% among controls. Conclusions: The miniclusters of prodromal features that emerged pre-school (ages 1–6), were “episodic” through childhood (7–12) and appeared to mimic adult recurrent illness. Prepubertal onset with mania did not occur. The pattern of prodromal symptoms has clinical relevance for its potential predictive value for onset with BPI disorder and early intervention.
The present study identifies the prevalence and types of comorbid psychiatric disorders associated with Asperger syndrome (AS)/high-functioning autism (HFA) in a combined community- and clinic-based ...sample of fifty 9- to 16-year-old subjects using the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version. The level of functioning was estimated using the Children’s Global Assessment Scale. The results support common (prevalence 74%) and often multiple comorbid psychiatric disorders in AS/HFA; behavioral disorders were shown in 44%, anxiety disorders in 42% and tic disorders in 26%. Oppositional defiant disorder, major depressive disorder and anxiety disorders as comorbid conditions indicated significantly lower levels of functioning. To target interventions, routine evaluation of psychiatric comorbidity in subjects with AS/HFA is emphasized.
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