•The visual P1 component is intensified to neutral stimuli in obsessive–compulsive disorder (OCD).•The intensified visual P1 is not predicted by sex or age or participants, nor depression, anxiety, ...or inattentiveness score.•Additional inquiry is necessary for determining if this finding relates to the sensory hypervigilance observed in OCD.
Existing studies have shown changes in attention and emotion processing of disorder-relevant visual stimuli in those with obsessive compulsive disorder (OCD). However, early visual processing in OCD has not been assessed, as previous studies did not examine the entire time course of visual processing but instead assessed potential differences in pre-determined visual evoked potentials (VEPs). This study investigates the entire visual processing stream in OCD compared to healthy age-matched controls (HC) using emotionally-neutral visual stimuli and a data-driven rather than hypothesis-driven approach.
35 HC and 26 participants with OCD underwent EEG recording while completing a modified Eriksen flanker task. Permutation-controlled t-tests were used to identify group differences in the data’s full time course of visual evoked potentials. Baseline-corrected amplitudes at time points where the groups were significantly different were analyzed using ANCOVAs with BDI, BAI, and SNAP-inattentiveness scores included as covariates.
This analysis identified enhanced P1 amplitudes to two visual stimuli (the initial flanker and the stimulus), corresponding to time windows of 65–93 ms and 157–187 ms post-flanker presentation in the OCD group compared to controls. Group (OCD vs. HC) was the strongest predictor of VEP amplitude during both time windows, with no significant influences of any covariates.
This study showed an enhanced P1 component in people with OCD to neutral visual stimuli, potentially reflecting either inefficient or excessive early visual processing in this population. Additional inquiry is necessary to determine whether altered visual processing is associated with the sensory hypervigilance observed in those with OCD.
This work identifies early visual processing alterations in OCD using neutral stimuli and a data-driven approach.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective: Tourette syndrome (TS) is a neuropsychiatric disorder with a genetic component that is highly comorbid with obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder ...(ADHD). However, the genetic relations between these disorders have not been clearly elucidated. This study examined the familial relations among TS, OCD, and ADHD in a large sample of TS families. Method: Parent-offspring concordance of TS, OCD, and ADHD was examined in 952 individuals from 222 TS-affected sib-pair families originally collected for genetic studies using logistic regression with generalized estimating equations to control for correlated data. Variance components methods were used to estimate the heritability and genetic and environmental correlations among TS, OCD, and ADHD. Bilineal families where both parents had TS or OCD were excluded. Results: OCD and ADHD were highly heritable in these TS families. There were significant genetic correlations between TS and OCD and between OCD and ADHD, but not between TS and ADHD. In addition, significant environmental correlations were found between TS and ADHD and between OCD and ADHD. Parental OCD + ADHD was associated with offspring OCD + ADHD. Conclusions: This study provides further evidence for a genetic relation between TS and OCD and suggests that the observed relation between TS and ADHD may due in part be to a genetic association between OCD and ADHD and in part due to shared environmental factors. (Contains 4 tables.)
Background:
Hikikomori, a form of social withdrawal first reported in Japan, may exist globally but cross-national studies of cases of hikikomori are lacking.
Aims:
To identify individuals with ...hikikomori in multiple countries and describe features of the condition.
Method:
Participants were recruited from sites in India, Japan, Korea and the United States. Hikikomori was defined as a 6-month or longer period of spending almost all time at home and avoiding social situations and social relationships, associated with significant distress/impairment. Additional measures included the University of California, Los Angeles (UCLA) Loneliness Scale, Lubben Social Network Scale (LSNS-6), Sheehan Disability Scale (SDS) and modified Cornell Treatment Preferences Index.
Results:
A total of 36 participants with hikikomori were identified, with cases detected in all four countries. These individuals had high levels of loneliness (UCLA Loneliness Scale M = 55.4, SD = 10.5), limited social networks (LSNS-6 M = 9.7, SD = 5.5) and moderate functional impairment (SDS M = 16.5, SD = 7.9). Of them 28 (78%) desired treatment for their social withdrawal, with a significantly higher preference for psychotherapy over pharmacotherapy, in-person over telepsychiatry treatment and mental health specialists over primary care providers. Across countries, participants with hikikomori had similar generally treatment preferences and psychosocial features.
Conclusion:
Hikikomori exists cross-nationally and can be assessed with a standardized assessment tool. Individuals with hikikomori have substantial psychosocial impairment and disability, and some may desire treatment.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
IMPORTANCE: 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. OBJECTIVE: To characterize the lifetime prevalence, clinical associations, ages of highest risk, and etiology of psychiatric comorbidity among individuals with TS. DESIGN, SETTING, AND PARTICIPANTS: 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). MAIN OUTCOMES AND MEASURES: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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.
Studies of the genetic basis of complex traits have demonstrated a substantial role for common, small-effect variant polygenic burden (PB) as well as large-effect variants (LEV, primarily rare). We ...identify sufficient conditions in which GWAS-derived PB may be used for well-powered rare pathogenic variant discovery or as a sample prioritization tool for whole-genome or exome sequencing. Through extensive simulations of genetic architectures and generative models of disease liability with parameters informed by empirical data, we quantify the power to detect, among cases, a lower PB in LEV carriers than in non-carriers. Furthermore, we uncover clinically useful conditions wherein the risk derived from the PB is comparable to the LEV-derived risk. The resulting summary-statistics-based methodology (with publicly available software, PB-LEV-SCAN) makes predictions on PB-based LEV screening for 36 complex traits, which we confirm in several disease datasets with available LEV information in the UK Biobank, with important implications on clinical decision-making.
Abstract Attitudes towards risk are highly consequential in clinical disorders thought to be prone to “risky behavior”, such as substance dependence, as well as those commonly associated with ...excessive risk aversion, such as obsessive-compulsive disorder (OCD) and hoarding disorder (HD). Moreover, it has recently been suggested that attitudes towards risk may serve as a behavioral biomarker for OCD. We investigated the risk preferences of participants with OCD and HD using a novel adaptive task and a quantitative model from behavioral economics that decomposes risk preferences into outcome sensitivity and probability sensitivity. Contrary to expectation, compared to healthy controls, participants with OCD and HD exhibited less outcome sensitivity, implying less risk aversion in the standard economic framework. In addition, risk attitudes were strongly correlated with depression, hoarding, and compulsion scores, while compulsion (hoarding) scores were associated with more (less) “rational” risk preferences. These results demonstrate how fundamental attitudes towards risk relate to specific psychopathology and thereby contribute to our understanding of the cognitive manifestations of mental disorders. In addition, our findings indicate that the conclusion made in recent work that decision making under risk is unaltered in OCD is premature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Individuals with hoarding disorder (HD) typically perform worse than peers on neuropsychological tasks involving visual perception. Functional neuroimaging shows diffusely increased activity in the ...visual cortex, consistent with inefficient visual processing in HD. The temporal locus of these inefficiencies in HD is unknown. This study examined the temporal unfolding of visual event‐related brain potentials (ERPs) to help better define the neurophysiological mechanisms underlying visual dysfunction in HD. Thirty‐three individuals with HD and 35 healthy controls (HC) were assessed using a 64‐channel EEG during a modified flanker task. Permutation‐controlled analyses were conducted to detect group differences in visual evoked ERPs on a millisecond‐to‐millisecond basis. Bayesian ANCOVAs and linear regressions that included hoarding and age were conducted to identify the best‐fit model for the identified VEPs, compared to a null model that included depression and anxiety severity. Three temporal regions (175 ms, 270 ms, and 440 ms), showed differences in amplitude between HD and HC and were consistent with ERP components N1, P1/N2, and a late negative slow wave (LNSW), respectively. After controlling for depression and anxiety, HD demonstrated an enhanced ERP amplitude at N1 and an attenuated amplitude in LNSW compared to HC but did not show differences at P1/N2. For the N1 and LNSW, there was also a primary effect of the interaction between hoarding and age. This study indicates that altered visuocortical reactivity in HD first occurs at the level of visuocortical processing after 170 ms, indicating alterations of middle and later, but not early, processing in occipitotemporal visual cortex.
New research has identified inefficacies with visual processing in individuals with hoarding disorder, but the neural time course of these differences is still unknown. We identified three temporal points of visual evoked potentials which demonstrated variations in individuals with hoarding at 175 ms, 270 ms, and 440 ms from initial visual stimuli presentation. This is the first evidence of exaggerated visuocortical reactivity in hoarding.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Gilles de la Tourette syndrome (GTS) is a neuropsychiatric movement disorder with reported abnormalities in various neurotransmitter systems. Considering the integral role of iron in neurotransmitter ...synthesis and transport, it is hypothesized that iron exhibits a role in GTS pathophysiology. As a surrogate measure of brain iron, quantitative susceptibility mapping (QSM) was performed in 28 patients with GTS and 26 matched controls. Significant susceptibility reductions in the patients, consistent with reduced local iron content, were obtained in subcortical regions known to be implicated in GTS. Regression analysis revealed a significant negative association of tic scores and striatal susceptibility. To interrogate genetic mechanisms that may drive these reductions, spatially specific relationships between susceptibility and gene-expression patterns from the Allen Human Brain Atlas were assessed. Correlations in the striatum were enriched for excitatory, inhibitory, and modulatory neurochemical signaling mechanisms in the motor regions, mitochondrial processes driving ATP production and iron‑sulfur cluster biogenesis in the executive subdivision, and phosphorylation-related mechanisms affecting receptor expression and long-term potentiation in the limbic subdivision. This link between susceptibility reductions and normative transcriptional profiles suggests that disruptions in iron regulatory mechanisms are involved in GTS pathophysiology and may lead to pervasive abnormalities in mechanisms regulated by iron-containing enzymes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In SOLO1, maintenance olaparib (300 mg twice daily) significantly improved progression-free survival (PFS) for patients with newly diagnosed
- and/or
-mutated advanced ovarian cancer compared with ...placebo (hazard ratio HR, 0.30; 95% CI, 0.23 to 0.41; median not reached
13.8 months). We investigated PFS in SOLO1 for subgroups of patients based on preselected baseline factors.
Investigator-assessed PFS subgroup analyses of SOLO1 included clinical response after platinum-based chemotherapy (complete CR or partial response PR), surgery type (upfront or interval surgery), disease status after surgery (residual or no gross residual disease), and BRCA mutation status (
or
). Additionally, we evaluated PFS in patients with stage III disease who underwent upfront surgery and had no gross residual disease. We also report objective response rate.
The risk of disease progression or death was reduced with olaparib compared with placebo by 69% (HR, 0.31; 95% CI, 0.21 to 0.46) and 63% (HR, 0.37; 95% CI, 0.24 to 0.58) in patients undergoing upfront or interval surgery; 56% (HR, 0.44; 95% CI, 0.25 to 0.77) and 67% (HR, 0.33; 95% CI, 0.23 to 0.46) in patients with residual or no residual disease after surgery; 66% (HR, 0.34; 95% CI, 0.24 to 0.47) and 69% in women with clinical CR or PR at baseline (HR, 0.31; 95% CI, 0.18 to 0.52); and 59% (HR, 0.41; 95% CI, 0.30 to 0.56) and 80% (HR 0.20; 95% CI, 0.10 to 0.37) in patients with a
or
mutation, respectively.
Patients with newly diagnosed advanced ovarian cancer achieve substantial benefit from maintenance olaparib treatment regardless of baseline surgery outcome, response to chemotherapy, or BRCA mutation type.
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