Anxiety and depression are leading causes of disability worldwide, yet individuals are often unable to access appropriate treatment. There is a need to develop effective interventions that can be ...delivered remotely. Previous research has suggested that emotional processing biases are a potential target for intervention, and these may be altered through brief training programs.
We report two experimental medicine studies of emotional bias training in two samples: individuals from the general population (
= 522) and individuals currently taking antidepressants to treat anxiety or depression (
= 212). Participants, recruited online, completed four sessions of EBT from their own home. Mental health and cognitive functioning outcomes were assessed at baseline, immediately post-training, and at 2-week follow-up.
In both studies, our intervention successfully trained participants to perceive ambiguous social information more positively. This persisted at a 2-week follow-up. There was no clear evidence that this change in emotional processing transferred to improvements in symptoms in the primary analyses. However, in both studies, there was weak evidence for improved quality of life following EBT amongst individuals with more depressive symptoms at baseline. No clear evidence of transfer effects was observed for self-reported daily stress, anhedonia or depressive symptoms. Exploratory analyses suggested that younger participants reported greater treatment gains.
These studies demonstrate the effectiveness of delivering a multi-session online training program to promote lasting cognitive changes. Given the inconsistent evidence for transfer effects, EBT requires further development before it can be considered as a treatment for anxiety and depression.
Cognitive dysfunction in schizophrenia is an important target for novel therapies. Effectively measuring the cognitive effects of compounds in clinical trials of schizophrenia could be a major ...barrier to drug development. The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) programme produced a consensus cognitive battery which is now widely used, however alternative assessments have advantages and disadvantages when compared with MATRICS. The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computerised assessment developed from animal behaviour paradigms and human neuropsychology. We review the utility of CANTAB according to MATRICS and CNTRICS recommendations. CANTAB tests have been used in more than 60 studies of psychotic disorders. Their neural bases are well understood through patient and neuroimaging studies and directly equivalent tests in rodents and non-human primates. The tests’ sensitivity to pharmacological manipulation is well established. Future studies should collect more data regarding psychometric properties in patients over short time periods, and should continue to study the tests’ relationships to functional outcomes. Computerised cognitive assessment may optimise the statistical power of cognitive trials by reducing measurement error and between-site variability and decreasing patient attrition through increased tolerability.
Stratified medicine approaches have potential to improve the efficacy of drug development for schizophrenia and other psychiatric conditions, as they have for oncology. Latent inhibition is a ...candidate biomarker as it demonstrates differential sensitivity to key symptoms and neurobiological abnormalities associated with schizophrenia. The aims of this research were to evaluate whether a novel latent inhibition task that is not confounded by alternative learning effects such as learned irrelevance, is sensitive to (1) an in-direct model relevant to psychosis using 7.5% carbon dioxide (CO
) inhalations to induce dopamine release
somatic anxiety and (2) a pro-cognitive pharmacological manipulation (
nicotine administration) for the treatment of cognitive impairment associated with schizophrenia. Experiment 1 used a 7.5% CO
challenge as a model of anxiety-induced dopamine release to evaluate the sensitivity of latent inhibition during CO
gas inhalation, compared to the inhalation of medical air. Experiment 2 examined the effect of 2 mg nicotine administration vs. placebo on latent inhibition to evaluate its sensitivity to a potential pro-cognitive drug treatment. Inhalation of 7.5% CO
raised self-report and physiological measures of anxiety and impaired latent inhibition, relative to a medical air control; whereas administration of 2 mg nicotine, demonstrated increased latent inhibition relative to placebo control. Here, two complementary experimental studies suggest latent inhibition is modified by manipulations that are relevant to the detection and treatment of schizophrenia. These results suggest that this latent inhibition task merits further investigation in the context of neurobiological sub-groups suitable for novel treatment strategies.
There is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders.
We measured the association between established ...psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up.
Principal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049).
The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.
Cognitive dysfunction is present in up to 70% of patients with multiple sclerosis (MS) and has been reported at all stages and in all subtypes of the disease. These deficits have been reported across ...a variety of cognitive domains, but are generally under-recognized and incompletely evaluated in routine clinical practice. The aim of this study was to investigate the spectrum of cognitive impairment in patients with MS presenting to a specialist MS clinic using the Cambridge Neuropsychological Test Automated Battery (CANTAB), administered on a touchscreen platform. Ninety MS patients completed computerized CANTAB tasks assessing working memory, executive function, processing speed, attention, and episodic memory. Scores were adjusted for age, sex, and level of education and classified as normal or impaired based on comparison with a large normative data pool. We also investigated the impact of clinical and demographic variables which could potentially influence cognitive performance including patient educational level (a proxy for cognitive reserve), disease status (duration, course, and severity of MS), and depression. CANTAB testing detected cognitive impairment in 40 patients (44% of the sample). The most frequently impaired domain was executive function, present in 55% of cognitively impaired individuals. Disease duration and severity were significantly associated with performance across various cognitive domains. Patients with depressive symptoms were also more likely to exhibit impaired processing speed. Results from this study confirm that cognitive impairment is common and occurs across a range of domains among MS patients attending routine clinical visits. CANTAB tasks provide a sensitive and practical approach to cognitive testing in MS patients as part of a holistic patient assessment.
Cognitive symptoms are an underrecognized aspect of depression that are often untreated. High-frequency cognitive assessment holds promise for improving disease and treatment monitoring. Although we ...have previously found it feasible to remotely assess cognition and mood in this capacity, further work is needed to ascertain the optimal methodology to implement and synthesize these techniques.
The objective of this study was to examine (1) longitudinal changes in mood, cognition, activity levels, and heart rate over 6 weeks; (2) diurnal and weekday-related changes; and (3) co-occurrence of fluctuations between mood, cognitive function, and activity.
A total of 30 adults with current mild-moderate depression stabilized on antidepressant monotherapy responded to testing delivered through an Apple Watch (Apple Inc) for 6 weeks. Outcome measures included cognitive function, assessed with 3 brief n-back tasks daily; self-reported depressed mood, assessed once daily; daily total step count; and average heart rate. Change over a 6-week duration, diurnal and day-of-week variations, and covariation between outcome measures were examined using nonlinear and multilevel models.
Participants showed initial improvement in the Cognition Kit N-Back performance, followed by a learning plateau. Performance reached 90% of individual learning levels on average 10 days after study onset. N-back performance was typically better earlier and later in the day, and step counts were lower at the beginning and end of each week. Higher step counts overall were associated with faster n-back learning, and an increased daily step count was associated with better mood on the same (P<.001) and following day (P=.02). Daily n-back performance covaried with self-reported mood after participants reached their learning plateau (P=.01).
The current results support the feasibility and sensitivity of high-frequency cognitive assessments for disease and treatment monitoring in patients with depression. Methods to model the individual plateau in task learning can be used as a sensitive approach to better characterize changes in behavior and improve the clinical relevance of cognitive data. Wearable technology allows assessment of activity levels, which may influence both cognition and mood.
Development of schizophrenia relates to both genetic and environmental factors. Functional deficits in many cognitive domains, including the ability to communicate in social interactions and impaired ...recognition of facial expressions, are common for patients with schizophrenia and might also be present in individuals at risk of developing schizophrenia. Here we explore whether an individual's polygenic risk score (PRS) for schizophrenia is associated with the degree of interregional similarities in blood oxygen level-dependent (BOLD) signal and gray matter volume of the face-processing network and whether the exposure to early adversity moderates this association. A total of 90 individuals (mean age 22 years, both functional and structural data available) were used for discovery analyses, and 211 individuals (mean age 26 years, structural data available) were used for replication of the structural findings. Both samples were drawn from the Northern Finland Birth Cohort 1986. We found that the degree of interregional similarities in BOLD signal and gray matter volume vary as a function of PRS; lowest interregional correlation (both measures) was observed in individuals with high PRS. We also replicated the gray matter volume finding. We did not find evidence for an interaction between early adversity and PRS on the interregional correlation of BOLD signal and gray matter volume. We speculate that the observed group differences in PRS-related correlations in both modalities may result from differences in the concurrent functional engagement of the face-processing regions over time, eg, via differences in exposure to social interaction with other people.
Genetic variants that contribute to the risk of psychiatric disorders may also affect normal variation in psychological function. Indeed, the behavioral effects of many genetic variants may be better ...understood as process-specific rather than disease-specific. A functional valine-to-methionine (Val(158)Met) polymorphism in the catechol-O-methyltransferase (COMT) gene has been associated with cognitive function and brain metabolic activity accompanying such tasks. Not all studies are consistent, and less is known about the effect of this polymorphism during development. The authors tested the hypothesis that a more informative COMT haplotype predicts normal cognitive development in a large population-based cohort of children enrolled in the Avon Longitudinal Study of Parents and Children.
Effects on verbal and performance IQ as well as verbal inhibition were assessed at age 8, and effects on working memory were assessed at age 10. From the five COMT single nucleotide polymorphisms (SNPs) genotyped, the effect of a functional three-SNP haplotype consisting of Val(158)Met and two synonymous SNPs (rs6269 and rs4818), which together exert a major influence on the level of COMT expression and enzyme activity, was evaluated.
This three-SNP haplotype predicted both verbal inhibition and working memory, and there was a genotype-by-sex interaction on verbal IQ. The effect of COMT genotype (diplotype) on cognition was curvilinear, which is consistent with the "inverted U" model of dopamine effect on frontal cortical efficiency. In addition, the SNP rs2075507 (previously rs2097603) was independently associated with verbal inhibition, while rs165599 showed no main cognitive effects. However, rs165599 showed a genotype-by-sex interaction with working memory.
Genetic variation at several loci in the COMT gene affects normal cognitive function in children.
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