Search

Executive functions (EF) deficits are hypothesized to be a core contributor to hoarding symptoms. EF have been studied in adult hoarding populations, but studies in youth are lacking. The current study compared multiple EF subdomains between youth with obsessive-compulsive disorder (OCD) and youth with OCD and hoarding symptoms. Forty youth (8–18 years old) with a primary diagnosis of OCD were recruited. Participants were divided by hoarding severity on the Child Saving Inventory (CSI) into either the “hoarding group” (upper 33.3%) or the “low-hoarding group” (lower 66.7%). Groups were compared on EF tasks of cognitive flexibility, decision-making, and inhibitory control. Youth in the hoarding group exhibited significantly higher cognitive flexibility and lowered perseveration than the low-hoarding group. Hoarding and low-hoarding groups did not differ in any other EF subdomain. Hoarding symptoms in youth with OCD were not associated with deficits in EF subdomains; instead, youth who hoard exhibited higher cognitive flexibility compared to youth with low hoarding symptoms.

Hoarding Disorder (HD) is a mental disorder characterized by persistent difficulties discarding or parting with possessions, often resulting in cluttered living spaces, distress, and impairment. Its etiology is largely unknown, but twin studies suggest that it is moderately heritable. In this study, we pooled phenotypic and genomic data from seven international cohorts (N = 27,651 individuals) and conducted a genome wide association study (GWAS) meta-analysis of parent- or self-reported hoarding symptoms (HS). We followed up the results with gene-based and gene-set analyses, as well as leave-one-out HS polygenic risk score (PRS) analyses. To examine a possible genetic association between hoarding symptoms and other phenotypes we conducted cross-trait PRS analyses. Though we did not report any genome-wide significant SNPs, we report heritability estimates for the twin-cohorts between 26–48%, and a SNP-heritability of 11% for an unrelated sub-cohort. Cross-trait PRS analyses showed that the genetic risk for schizophrenia and autism spectrum disorder were significantly associated with hoarding symptoms. We also found suggestive evidence for an association with educational attainment. There were no significant associations with other phenotypes previously linked to HD, such as obsessive-compulsive disorder, depression, anxiety, or attention-deficit hyperactivity disorder. To conclude, we found that HS are heritable, confirming and extending previous twin studies but we had limited power to detect any genome-wide significant loci. Much larger samples will be needed to further extend these findings and reach a “gene discovery zone”. To move the field forward, future research should not only include genetic analyses of quantitative hoarding traits in larger samples, but also in samples of individuals meeting strict diagnostic criteria for HD, and more ethnically diverse samples.

Background Neurocognitive impairments are common in OCD, although not well studied in children and youth with the disorder. Method Using the stop-signal task (SST), we measured response inhibition (stop-signal reaction time-SSRT), sustained attention (reaction time variability-RTV), reaction time (RT), and performance monitoring (post-error slowing-PES) in OCD cases and controls from two samples of children and youth. A Clinic OCD group (n = 171, aged 7-17 years) was recruited from a specialty clinic after rigorous assessment. A typically developing (Clinic TD, n = 157) group was enlisted through advertisement. A community OCD sample (Community OCD, n = 147) and controls (Community TD n = 13,832, aged 6-17 years) were recruited at a science museum. We also identified a community group with high OCD traits without an OCD diagnosis (Community High Trait; n = 125). Results Clinic OCD participants had longer SSRT and greater RTV than Clinic TD. These effects were greater in younger OCD participants and, for SSRT, in those on medication for OCD. The Community OCD group did not differ from Controls but was similar to the Clinic OCD group in ADHD and ASD comorbidity and medication usage. The Community High Trait group had longer SSRT and atypical PES suggesting that symptom severity predicts neurocognitive function. No group differences were found in RT. Conclusions In the largest study of neurocognitive performance in children with OCD to date, we found impaired response inhibition and sustained attention in OCD participants in comparison to typically developing peers. Performance was worse in younger OCD participants. In the community sample, participants with high OCD trait scores but no OCD diagnosis had impaired response inhibition and error processing, suggesting that OCD might be under-recognized.

We examined pathways from pre-existing psychosocial and economic vulnerability to mental health difficulties and stress in families during the COVID-19 pandemic. Data from two time points from a multi-cohort study initiated during the COVID-19 pandemic were used. Parents of children 6–18 years completed questionnaires on pre-COVID-19 socioeconomic and demographic factors in addition to material deprivation and stress due to COVID-19 restrictions, mental health, and family functioning. Youth 10 years and older also completed their own measures of mental health and stress. Using structural equation modelling, pathways from pre-existing vulnerability to material deprivation and stress due to COVID-19 restrictions, mental health, and family functioning, including reciprocal pathways, were estimated. Pre-existing psychosocial and economic vulnerability predicted higher material deprivation due to COVID-19 restrictions which in turn was associated with parent and child stress due to restrictions and mental health difficulties. The reciprocal effects between increased child and parent stress and greater mental health difficulties at Time 1 and 2 were significant. Reciprocal effects between parent and child mental health were also significant. Finally, family functioning at Time 2 was negatively impacted by child and parent mental health and stress due to COVID-19 restrictions at Time 1. Psychosocial and economic vulnerability is a risk factor for material deprivation during COVID-19, increasing the risk of mental health difficulties and stress, and their reciprocal effects over time within families. Implications for prevention policy and parent and child mental health services are discussed. Supplementary Information The online version contains supplementary material available at 10.1007/s12144-021-02459-z.

Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder that causes the patient to experience intrusive thoughts and/or to carry out repetitive, ritualized behaviors that are time consuming and impairing. OCD is familial and heritable. The genetic factors responsible for pathogenesis, however, remain largely unknown despite the numerous candidate gene studies conducted. Based on efficacy of serotonin reuptake inhibitors (SRIs) in treating OCD, serotonin system genes have been a dominant focus in OCD candidate gene studies. We review the most commonly studied candidate serotonin system gene variants (specifically in SLC6A4, HTR2A, HTR1B, and HTR2C) and their association with OCD. Although findings to date are mixed, serotonin transporter polymorphism 5-HTTLPR and HTR2A polymorphism rs6311 (or rs6313) are most consistently associated with OCD. Mixed findings may be the result of genetic complexity and phenotypic heterogeneity that future studies should account for. Homogenous patient subgroups reflecting OCD symptom dimensions, OCD subtypes, and sex should be used for gene discovery.

Background Serotonin system genes are commonly studied in obsessive-compulsive disorder (OCD), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive-compulsive (OC) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different OC trait dimensions and, furthermore, that they vary by sex. Methods Obsessive-compulsive trait dimensions (Cleaning/Contamination, Counting/Checking, Symmetry/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive-Compulsive Scale (TOCS). We genotyped candidate serotonin genes (directly genotyping the 5-HTTLPR polymorphism in SLC6A4 for 2018 individuals and using single nucleotide polymorphism (SNP) array data for genes SLC6A4, HTR2A, and HTR1B for 4711 individuals). We assessed the association between variants across these genes and each of the OC trait dimensions, within males and females separately. We analyzed OC traits as both (a) dichotomized based on a threshold value and (b) quantitative scores. Results The [LG + S] variant in 5-HTTLPR was significantly associated with hoarding in males (p-value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for 5-HTTLPR in females. Using SNP array data, there were significant findings for rumination in males for HTR2A SNPs (p-value of 1.04e-6 to 5.20e-6). Conclusions This represents the first genetic association study of OC trait dimensions in a community-based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in OCD should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group.

Background Population-based samples with valid, quantitative and genetically informative trait measures of psychopathology could be a powerful complement to case/control genetic designs. We report the convergent and predictive validity of the parent- and self-report versions of the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scale (SWAN). We tested if SWAN scores were associated with ADHD diagnosis, ADHD polygenic risk, as well as traits and polygenic risk for disorders that co-occur with ADHD: anxiety and obsessive-compulsive disorder (OCD). Methods We collected parent- and self-report SWAN scores in a sample of 15,560 children and adolescents (6-17 years) recruited at a science museum (Spit for Science sample). We established age and sex norms for the SWAN. Sensitivity-specificity analyses determined SWAN cut-points that discriminated those with and without a reported ADHD diagnosis. These cut-points were validated in a clinic sample (266 ADHD cases; 36 controls). Convergent validity was established using the Conners' parent- and self-report scales. Using Spit for Science participants with genome-wide data (n = 5,154), we tested if low, medium and high SWAN scores were associated with polygenic risk for ADHD, OCD and anxiety disorders. Results Parent- and self-report SWAN scores showed high convergent validity with Conners' scales and distinguished ADHD participants with high sensitivity and specificity in the Spit for Science sample. In a clinic sample, the Spit for Science cut-points discriminated ADHD cases from controls with a sensitivity of 84% and specificity of 92%. High SWAN scores and scores above the Spit for Science cut-points were significantly associated with polygenic risk for ADHD. SWAN scores were not associated with polygenic risk for OCD or anxiety disorders. Conclusions Our study supports the validity of the parent- and self-report SWAN scales and their potential in ADHD population-based genetic research.

Adjusting speed to maintain fast and accurate performance is critical to goal-directed behavior. This study examined development of response time adjustments in the stop signal task in 13,709 individuals aged 6-17 years (49.0% Caucasian) across four trial types: correct and incorrect go, successful (stop-inhibit), and failed (stop-respond) trials. People sped more after correct than incorrect go responses and slowed more after failed than successful stop trials. Greater slowing after stop-respond but less slowing after stop-inhibit trials was associated with better response inhibition. Response time adjustments were evident in children as young as age 6, developed throughout childhood, and plateaued by age 10. Results were consistent with the predictions of the error detection and shifting goal priority hypotheses for adjustments. [ABSTRACT FROM AUTHOR]

Background Most common disorders, including Attention-Deficit Hyperactivity Disorder (ADHD) and Obsessive-Compulsive Disorder (OCD), are likely extremes of traits that are widely distributed in the general population. People are more or less restless, inattentive, impulsive, obsessional and compulsive; only the extreme of these traits demarcate a clinical diagnosis. Thus, quantitative psychiatric traits, which often share polygenic risk with their relevant diagnosis, will help us discover genes for disorders. Quantitative cognitive traits that might mediate part of the genetic risk of psychiatric disorders (i.e., cognitive endophenotypes) are often less heterogeneous than a diagnosis which could help reduce noise to improve power for gene discovery. Based on these alternative approaches, we designed the Spit for Science study to examine the genomics of childhood psychiatric disorders using behavioural traits and a cognitive endophenotype relevant to ADHD and OCD in a large population-based sample of youth. Methods Spit for Science is a sample of 17,263 children (6-17 years of age) seen at a local science museum with measures of psychiatric traits and DNA from saliva. Quantitative data on ADHD traits using the Strengths and Weaknesses of ADHD and Normal Behavior (SWAN) scale, obsessive-compulsive (OC) traits using the Toronto Obsessive-Compulsive scale (TOCS) and response inhibition using the Stop-Signal task was collected. We genotyped unrelated Caucasians (n=5,636) using Illumina HumanCoreExome beadchips. For common variant analyses, we conducted standard quality control and used hypothesis-driven genome-wide association analyses (GWAS-HD) to test biological hypotheses for each trait. For the GWAS-HD, permutation tests were used to test the whole gene set for association with each trait respectively. Copy number variants (CNVs) were called using three algorithms and only CNV calls detected by two algorithms and at least 10kb in size were retained. We examined CNV burden for each trait individually. Results We have identified the first genome-wide finding for OC traits (rs7856850; p = 2.9 x 10-8, β = 0.13) replicated in an independent sample of youth screened for OCD. Genes involved in central nervous system development were significantly associated with both OC traits and response inhibition. Polygenic risk score analyses are forthcoming. ADHD traits were associated with increased CNV deletions while response inhibition was associated with more CNV duplications and longer CNV deletions. Discussion Several promising findings have emerged from the Spit for Science study. We identified the first genome-wide finding for OC traits, identified a biological pathway involved in both OC traits and response inhibition, and demonstrated the relationship between rare CNVs with ADHD traits and response inhibition. Results to date demonstrate the feasibility, power and utility of using quantitative-trait based and cognitive endophenotype approaches in community samples to help uncover the underlying genetic architecture of psychiatric disorders.

Although impulsive behavior is considered to peak during adolescence, relatively little empirical work has examined this issue. Sex differences in impulsivity across development are also poorly understood. We examined age and sex differences in impulsive action with a simplified version of the 5-choice serial reaction time test, using only 2 choices. Adolescent and adult male and female Sprague-Dawley rats were trained to respond to one of two possible brief light stimuli to receive a food reinforcer. Responding before the onset of the light stimulus (a premature response) was considered a measure of impulsive action. We also investigated age and sex differences in the impulsivity-inducing effects of drugs that (1) target neurotransmitter systems still developing during adolescence and (2) increase premature responding in adult rats. To this end, we examined the effects of increasing the inter-trial interval (ITI; 9 s) and amphetamine (dopamine releaser; 0, 0.25, 0.5 mg/kg; Experiment 1), Ro 63-1908 (glutamate NMDA receptor NR2B subunit antagonist; 0, 0.3, 1.0 mg/kg; Experiment 2 & 3), and nicotine (nicotinic receptor agonist and indirect dopamine releaser; 0, 0.15, 0.3 mg/kg; Experiment 3) on premature responding. Adolescent rats were more impulsive than adults. In response to a long ITI and amphetamine, adolescent males and adult females also made more premature responses compared to adult males. No consistent age or sex differences were observed for Ro 63-1908 or nicotine. These findings suggest that impulsive action is heightened in adolescents compared to adults. Further, age and sex differences in impulsive action may be mediated by dopamine.

Postpartum rats that had been previously raised in an artificial rearing (AR) apparatus, without their mothers or siblings during the preweaning period, show altered maternal responses towards their own offspring in adulthood. In mother-reared (MR) rats, nucleus accumbens (NAC) dopamine (DA) responses to pups evoke a robust sustained rise during the postpartum period and following treatment with estrogen/progesterone parturient-like hormones (Afonso et al., 2009). These MR females had siblings that received AR rearing with varying amounts of preweaning tactile stimulation (ARmin; ARmax). The present study examined NACshell DA responses to pup and food stimuli in these AR rats, and statistically compared them to their MR siblings. Microdialysis samples were collected from adult (90 days postnatal) AR females in different parity states (cycling vs. postpartum, Exp. 1), or after ovariectomy with different hormone treatments (sham vs. hormone, Exp. 2. After basal sample collection, pup and then food stimuli were individually presented to the females in the dialysis chamber. As with their MR siblings, basal DA concentrations were lower and pup-evoked DA responses greater in hormonally-primed AR females than in non-primed AR controls. Compared to their postpartum MR sisters (Exp. 1), AR rats had increased basal DA levels, reduced pup related DA elevations, and disrupted maternal behavior. The postpartum AR impairment in pup-evoked DA was reversed by additional pre-weaning tactile stimulation. Exogenous hormones (Exp. 2) eliminated AR impairments on pup-evoked DA responses. Although MR and AR siblings had comparable DA responses to food stimuli, upon reanalyzing MR data it was found that only postpartum dams had DA responses to pups greater than to food. These data suggest that that the hormonally induced suppression of basal DA levels may reflect saliency of pups which was greater in MR than in AR dams. Preweaning tactile stimulation could partially reverse these effects only in naturally cycling or parturient animals.

Vulnerability to the effects of drugs of abuse during adolescence may be related to altered incentive motivation, a process believed to be important in addiction. Incentive motivation can be seen when a neutral stimulus acquires motivational properties through repeated association with a primary reinforcer. We compared adolescent (postnatal day (PND) 24-50) and adult (PND 70) rats on a measure of incentive motivation: responding for a conditioned reinforcer (CR). Rats learned to associate the delivery of 0.1 ml of 10% sucrose with a conditioned stimulus (CS; light and tone); 30 pairings per day were given over 14 days. Then, we measured responding on a lever delivering the CS (now a CR) after injections of amphetamine (0, 0.25 or 0.5 mg/kg). We also examined responding for CR when the CS and sucrose were paired or unpaired during conditioning, and responding for the primary reinforcer (10% sucrose) in control experiments. Finally, we examined the effects of D(1) and D(2) dopamine receptor antagonists (SCH 39166 and eticlopride, respectively) and an opioid receptor antagonist (naltrexone) on responding for a CR in adolescent rats. Adolescents but not adults acquired responding for a CR, but adolescents responded less than adults for the primary reinforcer. Responding for a CR depended upon the pairing of the CS and sucrose during conditioning. Both dopamine and opioid receptor antagonists reduced responding for the CR. Therefore, incentive motivation may be enhanced in adolescents compared with adults, and incentive motivation may be mediated in part by both dopamine and opioid systems.

Abuse of methylphenidate (Ritalin) is rising, particularly during adolescence and early adulthood, but the long-term effects of its abuse during adolescence are unclear.In experiment 1, we examined the effect of adolescent methylphenidate self-administration (0.0625 mg/infusion), as compared with cocaine self-administration (0.125 mg/infusion), under a fixed ratio 1 schedule of reinforcement in male Sprague-Dawley rats during adolescence (postnatal day (PND) 32-47) on adult dopamine-mediated behaviors (PND70). These included responding for a conditioned reward (CR), a measure of incentive motivation, and amphetamine-induced locomotor activity. In experiment 2, we aimed to replicate and enhance the effects observed in experiment 1, and we also examined the effects of methylphenidate self-administration during adolescence on adult amphetamine-induced zif268 messenger ribonucleic acid (mRNA) expression.Adolescent rats self-administered both cocaine and methylphenidate. There was no effect of adolescent drug self-administration on adult baseline or amphetamine-induced responding for a CR. However, both adolescent methylphenidate and cocaine self-administration increased amphetamine-induced locomotion. Adolescent methylphenidate self-administration also enhanced amphetamine-induced zif268 mRNA expression in the nucleus accumbens.Our findings suggest that repeated, behaviorally contingent exposure to methylphenidate during adolescence enhances responsivity to the locomotor-stimulating and neuronal activating effects of amphetamine but not incentive motivation.

This study investigated the effects of prenatal stress and complete maternal deprivation, using the artificial rearing (AR) paradigm, on the expression of neural plasticity markers and hypothalamic-pituitary-adrenal (HPA) axis responsivity to stress. Rats were exposed to stress during gestation (day 10-21) and postnatally were either artificially reared (AR) or mother reared (MR). AR involves complete separation of the pup from both the dam and the litter throughout the pre-weaning period. In adulthood, we measured levels of corticosterone (CORT) in response to restraint stress. Also, we examined the expression of synaptophysin (SYN) and brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (MPFC) and the nucleus accumbens (Nacc), areas of the brain that mediate behavioral activation and attention, among other behaviors. Earlier work on the same rats indicated that these behavioral endpoints, such as locomotor activity and sensorimotor gating, are affected by our prenatal and postnatal manipulations. Prenatal stress decreased CORT at 20 and 90 min post-stressor in MR, but not in AR, animals. Also, in comparison to MR groups, AR decreased SYN and BDNF expression in the MPFC and Nacc. Additional somatosensory 'licking-like' stroking stimulation partially reversed the effects of AR. Prenatal stress did not have a robust main effect but affected the impact of the postnatal rearing condition on SYN expression and stress-induced CORT. These results suggest that both prenatal and postnatal adversities have an influence on HPA axis responsivity and alter the expression of plasticity related neuronal proteins.

Objective We assessed the prevalence and clinical correlates of hoarding, with and without obsessive-compulsive (OC) symptoms, in a community-based pediatric sample. Method We measured hoarding and OC symptoms using the Toronto Obsessive-Compulsive Scale (TOCS) in 16,718 youth aged 6 to 17 years in the community. We classified participants with high and low symptom counts for hoarding and OC into 4 groups: hoarding+OC; hoarding-only; OC-only; and control (no OC or hoarding symptoms). We compared these 4 groups on parent- or self-reported medical and psychiatric conditions, anxiety symptoms measured with the Child Behavior Checklist (CBCL), and attention-deficit/hyperactivity disorder (ADHD) symptoms measured with the Strengths and Weaknesses of Attention-Deficit/Hyperactivity Disorder Symptoms and Normal Behavior Scale (SWAN). Results Almost 10% of participants were in the high hoarding group. Of these participants, 40% did not fall into the high OC group. The prevalence of reported psychiatric disorders (e.g., ADHD, autism spectrum disorder, obsessive-compulsive disorder) was greater in the hoarding (hoarding+OC and hoarding-only) and OC groups (hoarding+OC and OC-only) than in the nonhoarding (OC-only and control) and non-OC groups (hoarding-only and control), respectively. ADHD, specifically inattentive, symptoms were more common in the hoarding-only than in the OC-only group while anxiety symptoms were more common in the OC-only than in the hoarding-only group. Conclusion In a community pediatric sample, hoarding symptoms occurred in both the presence and absence of obsessive-compulsive symptoms. Hoarding symptoms alone had some unique clinical correlates, in particular, more inattentive ADHD symptoms and fewer anxiety symptoms. These findings suggest that hoarding is distinct from OC traits in youth.

Background Genetics play an important role in ADHD and OCD but only a handful of mostly common risk variants have been identified in studies that compare ADHD/OCD patients with healthy controls. Copy number variants of high penetrance may play an important role in childhood neuropsychiatric disorders. Our current knowledge of CNVs in ADHD and OCD is based on relatively small samples of patients, and to interpret the significance of these CNVs we need to assess risk CNVs in the general population. To this end we determine the frequency of clinically relevant CNVs in a large population based sample of children and adolescents and examined the association of rare CNVs with ADHD and OCD traits. Methods Quantitative data on ADHD traits using the Strengths and Weaknesses of ADHD and Normal Behavior (SWAN) scale and OC traits using the Toronto Obsessive-Compulsive scale (TOCS) was collected from 17,263 youth (ages 6-17 years) from the community. We genotyped unrelated Caucasians (n=5,366) and East Asians (n=989) using Illumina HumanCoreExome beadchips. CNV were called using three algorithms: iPattern (ipn), PennCNV (pcnv), and QuantiSNP (qsnp) and a high confidence dataset was generated by retaining variants detected by two or more algorithms and at least 10kb in size. We defined rare variants as those with less than 0.1% frequency against our population controls. We plan to examine whether CNV burden, overall and within psychiatrically relevant gene sets (e.g., brain expression, brain development), is associated with ADHD and OCD traits. We will also test if individual CNVs are associated with ADHD and OCD traits. Results After stringent quality control, 4857 (90.5%) Caucasian and 933 (94.3%) East Asian samples remained. Total number of CNVs was 31,798 with a mean size of 117,316 base pairs and a maximum size of 7.1 MB. The average number of CNVs per participants was 6. We uncovered 9,836 rare variants, of which 4,151 are deletions and 5,687 are duplications. This comprises of 7,613 rare CNVs from European subjects (mean size = 139,856 kb) and 2,225 from Asian individuals (mean size =123,141 kb). This represented a mean of 1.57 and 2.38 rare CNVs per individuals, respectively. We identified a total of 15 different known genomic disorders from 41 subjects (0.7%) in this cohort. Quantitative trait results forthcoming. Discussion Our novel approach will help elucidate the rate of psychiatrically relevant CNVs in the general population and the association of these CNVs with ADHD and OCD. Our preliminary data shows the feasibility of CNV analysis and quality of CNV data from the HumanCoreExome array in a large population based sample. Financial Relationships I (or my spouse/partner) do have potential conflicts of interest to disclose.

Objective To describe the Toronto Obsessive-Compulsive Scale (TOCS), a novel 21-item parent- or self-report questionnaire that covers wide variation in obsessive-compulsive (OC) traits, and to evaluate its psychometric properties in a community-based pediatric sample. Method The TOCS was completed for 16,718 children and adolescents between the ages of 6 and 17 years in a community setting. Internal consistency, convergent validity with the Obsessive-Compulsive Scale of the Child Behaviour Checklist (CBCL-OCS), divergent validity with the Strengths and Weaknesses of ADHD (Attention-Deficit/Hyperactivity Disorder) Symptoms and Normal Behaviour Rating Scale (SWAN), interrater reliability, as well as sensitivity and specificity of the TOCS were assessed. Results The internal consistency of the 21 TOCS items was excellent (Cronbach’s α = 0.94). TOCS was moderately correlated with the CBCL-OCS (Spearman correlation = 0.51) and poorly correlated with the SWAN (Pearson correlation = 0.02). Sensitivity and specificity analyses indicated that a TOCS total score of greater than 0 successfully discriminated community-reported obsessive-compulsive disorder (OCD) cases from noncases. OC traits were continuously distributed both at the total score and dimensional level in our pediatric community sample. Conclusion TOCS is a multidimensional measure of OC traits in children and adolescents with sound psychometric properties. TOCS reveals that OC traits are common and continuously distributed in a community sample. TOCS may be a useful measure for studies of the characteristics and etiology of OC traits.

Despite its importance for development, relatively little is known about how allelic variation interactswith both pre- and postnatal stress. We examined the interaction between serotonin transporter (5-HTT)genotype, prenatal and postnatal stress on glucocorticoid receptor (GR) mRNA expression, corticosteroidstress responses, and behavior in adult male rats. Prenatal stress involved a daily restraint of pregnantdams from gestational Day 10–21. Postnatal stress involved raising pups after parturition either by theirmothers (MR) or in the artificial rearing (AR) paradigm, with or without additional “licking-like”stroking stimulation. 5-HTT genotype, hippocampal GR mRNA level, corticosteroid stress response, andbehaviors including startle response, prepulse inhibition (PPI), and locomotor activity were measured inadult male rat offspring. We found significant genotype by prenatal stress interactions for hippocampalGR mRNA levels and for the corticosterone stress responses in adulthood. In contrast, behavioralendpoints tended to be more clearly affected by an interaction between genotype and postnatal environ-ment. These findings suggest that allelic variation in the 5-HTT gene interacts with the prenatalenvironment to affect the hypothalamic-pituitary-adrenal (HPA) axis physiology and the postnatalenvironment to affect behavior. These results are the first to indicate a role for genetic variation in the5-HTT gene in physiology and behavior in the rat.Keywords: prenatal stress, acoustic startle, glucocorticoid receptor, HPA axis, rat maternal separation

Methylphenidate, which is used to treat attention deficit/hyperactivity disorder, increases extracellular dopamine by inhibiting the dopamine transporter. Methylphenidate has an abuse potential, and there are increasing reports of recreational use of methylphenidate. Little work has examined methylphenidate self-administration in rodent models.This work characterized intravenous methylphenidate self-administration in rats, determined whether dopamine mediates its reinforcing effects and examined the influence of route of administration on the ability of methylphenidate to reinstate extinguished drug-seeking behaviour.Rats were trained to self-administer methylphenidate (0.25 mg per infusion) via an intravenous catheter according to a fixed ratio 1 (FR1) or progressive ratio (PR) schedule. The effects of manipulating the dose of methylphenidate and of treatment with the dopamine D1 receptor antagonist SCH23390 or the dopamine D2 receptor antagonist eticlopride (both at 0.01 and 0.03 mg/kg) were examined. Finally, the ability of noncontingent administrations of methylphenidate (intraperitoneal [IP] or gavage) to reinstate extinguished drug-seeking behaviour was examined.Rats readily self-administered methylphenidate dose dependently on FR1 and PR schedules. Treatment with SCH23390 or eticlopride increased the number methylphenidate infusions taken by rats on the FR1 schedule and reduced breaking points on the PR schedule. Following extinction of drug-seeking behaviour, methylphenidate reinstated responding and was more effective at doing so when administered IP.These results demonstrate that intravenous methylphenidate is a reinforcer and that its reinforcing efficacy is related to increased dopamine activity at D1 and D2 receptors. Methylphenidate reinstates drug-seeking behaviour; the route of administration modifies this response suggesting that pharmacokinetic factors are important in determining methylphenidate-induced reinstatement.

Schizophrenia is associated with increased rates of substance abuse that are thought to be the result of changes in cortical and mesolimbic dopamine activity. Previous work has shown that gestational methylazoxymethanol acetate (MAM) treatment induces increased mesolimbic dopamine activity when given around the time of embryonic day 17 (ED17), suggesting that MAM treatment may model some aspects of schizophrenia. Given that increased dopaminergic activity facilitates aspects of drug self-administration and reinstatement of drug seeking, the current experiments sought to assess cocaine self-administration in MAM treated animals. Experiment 1 examined the acquisition of cocaine self-administration in ED17 MAM and saline treated rats using a sub-threshold dose of cocaine. In experiment 2 ED17 MAM and saline treated animals were trained to self-administer cocaine and were then assessed under varying doses of cocaine (dose-response), followed by extinction and drug-induced reinstatement of responding. A subset of these animals was trained on a win-shift radial maze task, designed to detect impairments in hippocampal-dependent memory. In experiment 3, MAM and saline treated animals were assessed on a progressive ratio schedule of cocaine delivery. Finally, in experiment 4 MAM and saline treated animals were assessed on cocaine-induced locomotor activity across a range of doses of cocaine. MAM treatment disrupted performance of the win-shift task but did not alter cocaine self-administration or cocaine-induced locomotion. Implications of these results for the MAM model of schizophrenia are discussed.

This study investigated the effects of prenatal stress and its interaction with artificial rearing (AR) on adult rat behavior. Pregnant dams underwent restraint stress from Gestational Day 10 to 21. After parturition, pups were raised by their mothers or in the AR paradigm, with or without stroking stimulation. In adulthood, rats were tested on prepulse inhibition (PPI), locomotor activity, elevated plus-maze, and spatial working memory. There were main effects and interactions of both prenatal stress and AR on activity. Additional stimulation reduced activity in nonstressed AR rats but increased activity in prenatally stressed AR rats. AR altered PPI and plus-maze behavior whereas additional stimulation partially reversed these effects. This study demonstrates that prenatal experiences can modulate the effects of postnatal treatments.

Background Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. Methods We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (