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This review aims to shed light on the symptoms of obsessive–compulsive disorder (OCD) with a focus on contamination fears. In addition, we will briefly review the current therapies for OCD and detail what their limitations are. A key focus will be on discussing how smartphone solutions may provide approaches to novel treatments, especially when considering global mental health and the challenges imposed by rural environments and limited resources; as well as restrictions imposed by world-wide pandemics such as COVID-19. In brief, research that questions this review will seek to address include: (1) What are the symptoms of contamination-related OCD? (2) How effective are current OCD therapies and what are their limitations? (3) How can novel technologies help mitigate challenges imposed by global mental health and pandemics/COVID-19.
Gastrointestinal (GI) symptoms such as pain, heartburn, abdominal bloating, diarrhea, and constipation occur in most individuals at some time or another. Numerous diagnostic studies and medical interventions are available, but often the problems continue. Eager for relief, nearly half of all patients with chronic GI symptoms turn to the many “complementary” or “alternative” approaches available to the public . This chapter reviews the options that have undergone testing, and summarizes those that are most likely to be of clinical benefit based on the quality of the studies. Many of the alternative approaches have undergone one form or another of clinical trial, but most often the data was either of poor quality or the studies were poorly controlled. Table 9.1 lists those approaches that are low risk and may be beneficial or have some supportive evidence. Table 9.2 lists those approaches that are clinically interesting but have insufficient supportive data to make a recommendation.
Many cognitive functions are under strong genetic control and twin studies have demonstrated genetic overlap between some aspects of cognition and schizophrenia. How the genetic relationship between specific cognitive functions and schizophrenia is influenced by IQ is currently unknown.
We applied selected tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to examine the heritability of specific cognitive functions and associations with schizophrenia liability. Verbal and performance IQ were estimated using The Wechsler Adult Intelligence Scale-III and the Danish Adult Reading Test. In total, 214 twins including monozygotic (MZ = 32) and dizygotic (DZ = 22) pairs concordant or discordant for a schizophrenia spectrum disorder, and healthy control pairs (MZ = 29, DZ = 20) were recruited through the Danish national registers. Additionally, eight twins from affected pairs participated without their sibling.
Significant heritability was observed for planning/spatial span (h2 = 25%), self-ordered spatial working memory (h2 = 64%), sustained attention (h2 = 56%), and movement time (h2 = 47%), whereas only unique environmental factors contributed to set-shifting, reflection impulsivity, and thinking time. Schizophrenia liability was associated with planning/spatial span (rph = −0.34), self-ordered spatial working memory (rph = −0.24), sustained attention (rph = −0.23), and set-shifting (rph = −0.21). The association with planning/spatial span was not driven by either performance or verbal IQ. The remaining associations were shared with performance, but not verbal IQ.
This study provides further evidence that some cognitive functions are heritable and associated with schizophrenia, suggesting a partially shared genetic etiology. These functions may constitute endophenotypes for the disorder and provide a basis to explore genes common to cognition and schizophrenia.
Data related to brain function may have the potential to improve the reliability and validity of assessments for the aetiologically and clinically heterogeneous syndrome of attention-deficit/hyperactivity disorder (ADHD). This study investigated associations between questionnaire assessments of behavioural features of adults with ADHD and an aspect of neurocognitive performance which has been reported to be impaired in adults with ADHD.
Fifty-nine adult patients with a DSM-IV diagnosis of ADHD, and their informants, completed questionnaires related to aspects of severity of ADHD. Associations were examined between questionnaire ratings and performance on a computer-administered task of spatial working memory (SWM).
Correlations between ratings of ADHD and SWM indicated moderate but significant correlations for patients' ratings, but not for informants' ratings. Also, patients who reported a past history of ‘self-harm’ (N = 33) had a significantly worse mean performance on both measures of SWM (p = 0.004, 0.003).
The results indicate that aspects of impulsivity, i.e. self-ratings of ‘emotive’ behaviour (involving rapid response to stimuli and marked reactivity of mood) and of past ‘self-harm’, show relatively strong associations with SWM performance in adults selected on the basis of an ADHD diagnosis. A profile of neurocognitive performances may have a role in the assessment of ADHD.
Atomoxetine, a highly selective noradrenaline reuptake inhibitor, shows efficacy in the treatment of ADHD. Despite evidence that atomoxetine improved inhibitory control in animals and healthy volunteers, studies had yet to explore short-term cognitive effects in patients with ADHD.
The cognitive effects of a single oral dose of atomoxetine (60mg) were evaluated in n=22 adults with DSM-IV ADHD, using a within-subject placebo-controlled double-blind design. Assessment included the stop-signal test and Rapid Visual Information Processing test from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Cardiovascular responses were monitored. Normative cognitive data from 20 healthy volunteers were collected for comparison.
Atomoxetine was associated with shorter stop-signal reaction times (p<0.05) and lower numbers of commission errors (p<0.05) on the sustained attention task in the ADHD patients.
These findings suggest that atomoxetine exerts beneficial effects on aspects of inhibitory control in ADHD, which may belie the efficacy of this medication in the treatment of impulsive features of the disorder. These findings also have potential clinical implications for other impulse dysregulation disorders such as trichotillomania and Tourette's Syndrome.
Although neuroimaging studies suggest brain regional abnormalities in depressive disorders, it remains unclear whether abnormalities are present at illness onset or reflect disease progression.
We hypothesized that cerebral variations were present in adolescents with subthreshold depression known to be at high risk for later full-blown depression.
We examined brain structural and diffusion-weighted magnetic resonance images of adolescents with subthreshold depression.
The participants were extracted from the European IMAGEN study cohort of healthy adolescents recruited at age 14. Subthreshold depression was defined as a distinct period of abnormally depressed or irritable mood, or loss of interest, plus two or more depressive symptoms but without diagnosis of Major Depressive Episode. Comparisons were performed between adolescents meeting these criteria and control adolescents within the T1-weighted imaging modality (118 and 475 adolescents respectively) using voxel-based morphometry and the diffusion tensor imaging modality (89 ad 422 adolescents respectively) using tract-based spatial statistics. Whole brain analyses were performed with a statistical threshold set to p< 0.05 corrected for multiple comparisons.
Compared with controls, adolescents with subthreshold depression had smaller gray matter volume in caudate nuclei, medial frontal and cingulate cortices; smaller white matter volume in anterior limb of internal capsules, left forceps minor and right cingulum; and lower fractional anisotropy and higher radial diffusivity in the genu of corpus callosum.
The findings suggest that adolescents with subthreshold depression have volumetric and microstructural gray and white matter changes in the emotion regulation frontal-striatal-limbic network.
Serotonin is well known to affect the multifaceted construct of impulsivity. Lowering brain serotonin levels is shown to increase impulsive choice in delay-discounting tasks (1) but improves response inhibition in stop-signal paradigms. (2) Administration of the antidepressant citalopram in healthy people increases tendency to perform go choices in a Go/No-Go task independent of outcome valence (3). It is rather unclear thought how serotonergic neurotransmission affects several aspects of cognition. We administered a single dose of 20 mg escitalopram, a selective serotonin reuptake inhibitor, to 66 healthy participants, aged 18–45 years old, in a double-blind, randomized, placebo-controlled, parallel-groups study. Acute escitalopram administration had a beneficial effect on inhibitory control with reduced stop-signal reaction time observed in the treatment group. Participants made significantly more errors in a probabilistic learning task and had lower accuracy during the discrimination stage in an instrumental learning task thus indicating a learning impairment. More errors in the CANTAB intra-extra dimensional set shift task were also observed in the escitalopram-treated group. Our findings following acute administration of a clinically relevant dose of escitalopram show a dissociate role for serotonin in modulating cognition mediated by a potentially differential modulation of fronto-striatal loops.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Goal-directed control guides optimal decision-making and it is an important cognitive faculty that protects against developing habits. Previous studies have found some evidence of goal-directed deficits when healthy individuals are stressed, and in psychiatric conditions characterised by compulsive behaviours and anxiety. Here, we tested if goal-directed control is affected by state anxiety, which might explain the former results.
We carried out a causal test of this hypothesis in two experiments (between-subject N = 88; within-subject N = 50) that used the inhalation of hypercapnic gas (7.5% CO2) to induce an acute state of anxiety in healthy volunteers. In a third experiment (N = 1413), we used a correlational design to test if real-life anxiety-provoking events (panic attacks, stressful events) are associated with impaired goal-directed control.
In the former two causal experiments, we induced a profoundly anxious state, both physiologically and psychologically, but this did not affect goal-directed performance. In the third, correlational, study, we found no evidence for an association between goal-directed control, panic attacks or stressful life eventsover and above variance accounted for by trait differences in compulsivity.
In sum, three complementary experiments found no evidence that anxiety impairs goal-directed control in human subjects.
Trends in utilization of Emergency Medical Services (EMS) systems can be used to extrapolate future use of an EMS system, which will be valuable for the budgeting and planning of finances and resources. The best model for incorporation of seasonal and regional fluctuations in utilization to predict future utilization is unknown.
Authors aimed to trend patterns of utilization in a regional EMS system to identify the needs of a growing population and to allow for a better understanding of how the EMS system is used on a basis of call volume and frequency of EMS transportation. The authors then used a best-fitting prediction model approach to show how the studied EMS system will be used in future years.
Systems data were retrospectively extracted by using the electronic medical records of the studied EMS system and its computer-assisted dispatch (CAD) database from 2010 through 2017. All EMS dispatches entering the system’s 9-1-1 public service access point were captured. Annual utilization data were available from 2010 through 2017, while quarterly data were available only from 2013 through 2017. The 9-1-1 utilization per capita, Advanced Life Support (ALS) utilization per capita, and ALS cancel rates were calculated and trended over the study period. The methods of prediction were assessed through a best-fitting model approach, which statistically suggested that Additive Winter’s approach (SAS) was the best fit to determine future utilization and ALS cancel rates.
Total 9-1-1 call volume per capita increased by 32.46% between 2010 and 2017, with an average quarterly increase of 0.78% between 2013 and 2017. Total ALS call volume per capita increased by 1.93% between 2010 and 2017. Percent ALS cancellations (cancelled en route to scene) increased by eight percent between 2010 and 2017, with an average quarterly increase of 0.42% (2013–2017). Predictions to end of 2019 using Additive Winter’s approach demonstrated increasing trends in 9-1-1 call volume per capita (R2 = 0.47), increasing trends of ALS utilization per capita (R2 = 0.71), and increasing percent ALS cancellation (R2 = 0.93). Each prediction showed increasing future trends with a 95% confidence interval.
The authors demonstrate paramount per capita increases of 9-1-1 call volume in the studied ALS system. There are concomitant increases of ALS cancellations prior to arrival, which suggests a potential burden on this regional ALS response system.
Data quality in survey research remains a paramount concern for those studying mass political behavior. Because surveys are conducted in increasingly diverse contexts around the world, ensuring that best practices are followed becomes ever more important to the field of political science. Bringing together insights from surveys conducted in more than 80 countries worldwide, this article highlights common challenges faced in survey research and outlines steps that researchers can take to improve the quality of survey data. Importantly, the article demonstrates that with the investment of the necessary time and resources, it is possible to carry out high-quality survey research even in challenging environments in which survey research is not well established.
Potentiometric titrations are a widely used technique to quantify proton-active functional groups on microorganisms, their exudates, biominerals, and biofilms. In this chapter, we provide a step-by-step introduction to the preparation of microbial cells for the determination of proton buffering capacity using modern autotitration systems. Following a discussion of how to process titration data and plot titration curves, we review commonly used thermodynamic approaches to model titration curves in order to calculate cell wall functional group acidity constants and corresponding site concentrations. In geomicrobiology, protonation models are primarily used as a basis for the development of surface complexation models that can predict the adsorption of charged species such as metals to biomass. The case example that follows outlines the development of a surface complexation model for the adsorption of cadmium to a species of the marine cyanobacterium Synechococcus, using a protonation model developed from titration data as its basis. In the last section, we introduce the reader to other analytical tools that are complementary to titration results, and discuss a few common complications to the titration approach when it is applied to natural materials.
Objectives: Prior studies have found associations between visual acuity (VA) and cognitive function. However, these studies used a limited range of cognitive measures and did not control for cardiovascular disease risk factors (CVD-RFs) and baseline function. The primary objective of this study was to analyze the associations of VA and cognitive performance using a thorough neuropsychological test battery. Methods: This study used community-dwelling sample data across the sixth (2001–2006) and seventh (2006–2010) waves of the Maine-Syracuse Longitudinal Study (n=655). Wave 6 VA as measured by the Snellen Eye Test was the primary predictor of wave 6 and wave 7 Global cognitive performance, Visual-Spatial Organization and Memory, Verbal Episodic Memory, Working Memory, Scanning and Tracking, and Executive Function. Additionally, VA was used to predict longitudinal changes in wave 7 cognitive performance (wave 6 performance adjusted). We analyzed these relationships with multiple linear and logistic regression models adjusted for age, sex, education, ethnicity, depressive symptoms, physical function deficits in addition to CVD-RFs, chronic kidney disease, homocysteine, continuous systolic blood pressure, and hypertension status. Results: Adjusted for demographic covariates and CVD-RFs, poorer VA was associated with concurrent and approximate 5-year declines in Global cognitive function, Visual-Spatial Organization and Memory, and Verbal Episodic Memory. Discussion: VA may be used in combination with other screening measures to determine risk for cognitive decline. (JINS, 2018, 24, 1–9)
Youths with obsessive–compulsive disorder (OCD) experience severe distress and impaired functioning at school and at home. Critical cognitive domains for daily functioning and academic success are learning, memory, cognitive flexibility and goal-directed behavioural control. Performance in these important domains among teenagers with OCD was therefore investigated in this study.
A total of 36 youths with OCD and 36 healthy comparison subjects completed two memory tasks: Pattern Recognition Memory (PRM) and Paired Associates Learning (PAL); as well as the Intra-Extra Dimensional Set Shift (IED) task to quantitatively gauge learning as well as cognitive flexibility. A subset of 30 participants of each group also completed a Differential-Outcome Effect (DOE) task followed by a Slips-of-Action Task, designed to assess the balance of goal-directed and habitual behavioural control.
Adolescent OCD patients showed a significant learning and memory impairment. Compared with healthy comparison subjects, they made more errors on PRM and PAL and in the first stages of IED involving discrimination and reversal learning. Patients were also slower to learn about contingencies in the DOE task and were less sensitive to outcome devaluation, suggesting an impairment in goal-directed control.
This study advances the characterization of juvenile OCD. Patients demonstrated impairments in all learning and memory tasks. We also provide the first experimental evidence of impaired goal-directed control and lack of cognitive plasticity early in the development of OCD. The extent to which the impairments in these cognitive domains impact academic performance and symptom development warrants further investigation.
We study the dynamics of a domain wall under the influence of applied magnetic fields in a one-dimensional ferromagnetic nanowire, governed by the Landau–Lifshitz–Gilbert equation. Existence of travelling-wave solutions close to two known static solutions is proven using implicit-function-theorem-type arguments.
Human-induced pluripotent stem cells (iPSCs) offer a novel, timely approach for investigating the aetiology of neuropsychiatric disorders. Although we are starting to gain more insight into the specific mechanisms that cause Alzheimer's disease and other forms of dementia, this has not resulted in therapies to slow the pathological processes. Animal models have been paramount in studying the neurobiological processes underlying psychiatric disorders. Nonetheless, these human conditions cannot be entirely recapitulated in rodents. Human cell models derived from patients’ cells now offer new hope for improving our understanding of the early molecular stages of these diseases, through to validating therapeutics. The impact of dementia is increasing, and a new model to investigate the early stages of this disease is heralded as an essential, new platform for translational research. In this paper, we review current literature using iPSCs to study Alzheimer's disease, describe drug discovery efforts using this platform, and discuss the future potential for this technology in psychiatry research.
Comparing genotype results of tuberculosis (TB) isolates from individuals diagnosed with TB can support or refute transmission; however, these conclusions are based upon the criteria used to define a genotype match. We used a genotype-match definition which allowed for variation in IS6110 restriction fragment length polymorphism (RFLP) to support transmission between epidemiologically linked persons. Contacts of individuals with infectious TB (index cases) diagnosed in New York City from 1997 to 2003 who subsequently developed TB (contact cases) from 1997 to 2007 were identified. For each contact case and index case (case-pair), isolate genotypes (spoligotype and RFLP results) were evaluated. Isolates from case-pairs were classified as exact or non-exact genotype match. Genotypes from non-exact match case-pairs were reviewed at the genotyping laboratory to determine if the isolates met the near-genotype-match criteria (exactly matching spoligotype and similar RFLP banding patterns). Of 118 case-pairs identified, isolates from 83 (70%) had exactly matching genotypes and 14 (12%) had nearly matching genotypes (supporting transmission), while the remaining 21 (18%) case-pairs had discordant genotypes (refuting transmission). Using identical genotype-match criteria for isolates from case-pairs epidemiologically linked through contact investigation may lead to underestimation of transmission. TB programmes should consider the value of expanding genotype-match criteria to more accurately assess transmission between such cases.
Recurrent glioblastoma (GBM) has an unmet need for effective therapies. Toca 511 (vocimagene amiretrorepvec), a retroviral replicating vector with the transgene cytosine deaminase, selectively infects, persists and spreads in tumor. Subsequent oral administration of 5-fluorocytosine (Toca FC) produces 5-fluorouracil (5-FU) within infected cells. 5-FU kills cancer cells and myeloid derived suppressor cells, inducing robust antitumor immune responses in animal models. In 2 Phase 1 studies, Toca 511 was administered into the cavity wall after surgical resection (NCT01470794) or intratumoral injection by biopsy needle (NCT01156584). To provide context to the results observed, subjects were compared to an external lomustine treated control (Courtesy Denovo Biopharma; Wick 2010). Treatment with Toca 511/Toca FC from 2 Phase I studies showed significant improvement in OS HR equals to 0.48, p less than 0.001, with similar effect in the surgical resection (OS HR 0.45, p equals to 0.003) and intratumoral injection (OS HR 0.56, p equals to 0.060). Fewer related greater or equal to Grade 3 adverse events (AEs) were reported for Toca 511/Toca FC (2.5 percent) vs. lomustine (36.9 percent). There was a virtual absence of hematologic toxicity for Toca 511/Toca FC vs. lomustine (Grade greater or equal to 3 thrombocytopenia 23.8 percent). Discontinuations for AEs occurred in 0percent for Toca 511/Toca FC vs. 4.8 percent for lomustine. Toca 511 is surgically delivered and treatment-emergent AEs regardless of attribution included incision site pain (20 percent), procedural pain (12.5 percent), and wound infection (5 percent) vs. 0percent, 1.2 percent, 1.2 percent respectively for lomustine. Toca 511/Toca FC significantly improved survival and safety relative to lomustine. A Phase 2/3 trial has launched (NCT02414165).
There is evidence of executive function impairment in obsessive compulsive disorder (OCD) that potentially contributes to symptom development and maintenance. Nevertheless, the precise nature of these executive impairments and their neural basis remains to be defined.
We compared stopping and shifting, two key executive functions previously implicated in OCD, in the same task using functional magnetic resonance imaging, in patients with virtually no co-morbidities and age-, verbal IQ- and gender-matched healthy volunteers. The combined task allowed direct comparison of neural activity in stopping and shifting independent of patient sample characteristics and state variables such as arousal, learning, or current symptom expression.
Both OCD patients and controls exhibited right inferior frontal cortex activation during stopping, and left inferior parietal cortex activation during shifting. However, widespread under-activation across frontal-parietal areas was found in OCD patients compared to controls for shifting but not stopping. Conservative, whole-brain analyses also indicated marked divergent abnormal activation in OCD in the caudate and thalamus for these two cognitive functions, with stopping-related over-activation contrasting with shift-related under-activation.
OCD is associated with selective components of executive function, which engage similar common elements of cortico-striatal regions in different abnormal ways. The results implicate altered neural activation of subcortical origin in executive function abnormalities in OCD that are dependent on the precise cognitive and contextual requirements, informing current theories of symptom expression.