Double-dipping revisited

Robust conclusions require rigorous statistics. In 2009 a seminal paper described the dangers and prevalence of double-dipping in neuroscience. Ten years on, I consider progress toward statistical rigor in neuroimaging

Trajectories of depression and generalised anxiety symptoms over the course of cognitive behaviour therapy in primary care: an observational, retrospective cohort

Background:Cognitive-behavioural therapy (CBT) has been shown to be an effective treatment for depression and anxiety. However, most research has focused on the sum scores of symptoms. Relatively little is known about how individual symptoms respond.Methods:Longitudinal models were used to explore how depression and generalised anxiety symptoms behave over the course of CBT in a retrospective, observational cohort of patients from primary care settings (n = 5306). Logistic mixed models were used to examine the probability of being symptom-free across CBT appointments, using the 9-item Patient Health Questionnaire and the 7-item Generalised Anxiety Disorder scale as measures.Results:All symptoms improve across CBT treatment. The results suggest that low mood/hopelessness and guilt/worthlessness improved quickest relative to other depressive symptoms, with sleeping problems, appetite changes, and psychomotor retardation/agitation improving relatively slower. Uncontrollable worry and too much worry were the anxiety symptoms that improved fastest; irritability and restlessness improved the slowest.Conclusions:This research suggests there is a benefit to examining symptoms rather than sum scores alone. Investigations of symptoms provide the potential for precision psychiatry and may explain some of the heterogeneity observed in clinical outcomes when only sum scores are considered

Self-processing in relation to emotion and reward processing in depression

BACKGROUND: Depression is characterised by a heightened self-focus, which is believed to be associated with differences in emotion and reward processing. However, the precise relationship between these cognitive domains is not well understood. We examined the role of self-reference in emotion and reward processing, separately and in combination, in relation to depression.METHODS: Adults experiencing varying levels of depression (n = 144) completed self-report depression measures (PHQ-9, BDI-II). We measured self, emotion and reward processing, separately and in combination, using three cognitive tasks.RESULTS: When self-processing was measured independently of emotion and reward, in a simple associative learning task, there was little association with depression. However, when self and emotion processing occurred in combination in a self-esteem go/no-go task, depression was associated with an increased positive other bias [b = 3.51, 95% confidence interval (CI) 1.24-5.79]. When the self was processed in relation to emotion and reward, in a social evaluation learning task, depression was associated with reduced positive self-biases (b = 0.11, 95% CI 0.05-0.17).CONCLUSIONS: Depression was associated with enhanced positive implicit associations with others, and reduced positive learning about the self, culminating in reduced self-favouring biases. However, when self, emotion and reward processing occurred independently there was little evidence of an association with depression. Treatments targeting reduced positive self-biases may provide more sensitive targets for therapeutic intervention and potential biomarkers of treatment responses, allowing the development of more effective interventions.</p

Low statistical power in biomedical science:a review of three human research domains

Studies with low statistical power increase the likelihood that a statistically significant finding represents a false positive result. We conducted a review of meta-analyses of studies investigating the association of biological, environmental or cognitive parameters with neurological, psychiatric and somatic diseases, excluding treatment studies, in order to estimate the average statistical power across these domains. Taking the effect size indicated by a meta-analysis as the best estimate of the likely true effect size, and assuming a threshold for declaring statistical significance of 5%, we found that approximately 50% of studies have statistical power in the 0–10% or 11–20% range, well below the minimum of 80% that is often considered conventional. Studies with low statistical power appear to be common in the biomedical sciences, at least in the specific subject areas captured by our search strategy. However, we also observe evidence that this depends in part on research methodology, with candidate gene studies showing very low average power and studies using cognitive/behavioural measures showing high average power. This warrants further investigation

Inhibitory control of positive and negative information and adolescent depressive symptoms:a population-based cohort study

BACKGROUND: Large population-based cohort studies of neuropsychological factors that characterise or precede depressive symptoms are rare. Most studies use small case-control or cross-sectional designs, which may cause selection bias and cannot test temporality. In a large UK population-based cohort, we investigated cross-sectional and longitudinal associations between inhibitory control of positive and negative information and adolescent depressive symptoms.METHODS: Cohort study of 2328 UK adolescents who completed an affective go/no-go task at age 18. Depressive symptoms were assessed with the Clinical Interview Schedule Revised (CIS-R) and short Mood and Feeling Questionnaire (sMFQ) at age 18, and with the sMFQ 1 year later (age 19). Analyses were multilevel and traditional linear regressions, before and after adjusting for confounders.RESULTS: Cross-sectionally, we found little evidence that adolescents with more depressive symptoms made more inhibitory control errors [after adjustments, errors increased by 0.04% per 1 s.d. increase in sMFQ score (95% confidence interval 0.02-0.06)], but this association was not observed for the CIS-R. There was no evidence for an influence of valence. Longitudinally, there was no evidence that reduced inhibitory control was associated with future depressive symptoms.CONCLUSIONS: Inhibitory control of positive and negative information does not appear to be a marker of current or future depressive symptoms in adolescents and would not be a useful target in interventions to prevent adolescent depression. Our lack of convincing evidence for associations with depressive symptoms suggests that the affective go/no-go task is not a promising candidate for future neuroimaging studies of adolescent depression.</p

Inhibitory control of positive and negative information and adolescent depressive symptoms:a population-based cohort study

BACKGROUND: Large population-based cohort studies of neuropsychological factors that characterise or precede depressive symptoms are rare. Most studies use small case-control or cross-sectional designs, which may cause selection bias and cannot test temporality. In a large UK population-based cohort, we investigated cross-sectional and longitudinal associations between inhibitory control of positive and negative information and adolescent depressive symptoms. METHODS: Cohort study of 2328 UK adolescents who completed an affective go/no-go task at age 18. Depressive symptoms were assessed with the Clinical Interview Schedule Revised (CIS-R) and short Mood and Feeling Questionnaire (sMFQ) at age 18, and with the sMFQ 1 year later (age 19). Analyses were multilevel and traditional linear regressions, before and after adjusting for confounders. RESULTS: Cross-sectionally, we found little evidence that adolescents with more depressive symptoms made more inhibitory control errors [after adjustments, errors increased by 0.04% per 1 s.d. increase in sMFQ score (95% confidence interval 0.02-0.06)], but this association was not observed for the CIS-R. There was no evidence for an influence of valence. Longitudinally, there was no evidence that reduced inhibitory control was associated with future depressive symptoms. CONCLUSIONS: Inhibitory control of positive and negative information does not appear to be a marker of current or future depressive symptoms in adolescents and would not be a useful target in interventions to prevent adolescent depression. Our lack of convincing evidence for associations with depressive symptoms suggests that the affective go/no-go task is not a promising candidate for future neuroimaging studies of adolescent depression

Possible Association of APOE Genotype with Working Memory in Young Adults

Possession of the ε4 allele of the Apolipoprotein E (APOE) gene is associated with an increased risk of Alzheimer's disease. Early adult life effects of ε4 are less well understood. Working memory has been relatively little studied (compared to episodic memory) in relation to APOE genotype despite its importance in cognitive functioning. Our hypothesis was that ε4 would lead to an impairment in working memory in young adults.We studied working memory using a computerised n-back task in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 18. Data was available for 1049-1927 participants and for the 2- and 3-back versions of the task. Using multiple and multi-level regression controlling for important confounders we examined the association between APOE genotype on accuracy and reaction times.There was no evidence of a genotype effect on accuracy when the two difficulty levels were examined separately. There was some evidence to support a deleterious effect of the ε4 allele on n-back accuracy in the multi-level regression. There was weak evidence that the ε22 group were less accurate but the numbers were very low in this group. The ε34 group had faster reaction times than the reference ε33 group in all adjusted analyses but the ε44 group were only faster in the 3-back condition in multi-level analyses.There was no evidence of benefit in ε4 carriers, but there was some evidence of a detrimental effect on working memory in this large study

Depression screening using a non-verbal self-association task:A machine-learning based pilot study

Background: Effective screening is important to combat the raising burden of depression and opens a critical time window for early intervention. Clinical use of non-verbal depression screening is nascent, yet a promising and viable candidate to supplement verbal screening. Differential self- and emotion-processing in depression patients were previously reported by non-verbal behavioural assessments, corroborated by neuroimaging findings of distinct neuroanatomical markers. Thus non-verbal validated brain-behaviour based self-emotion-related assessment data reflect physiological differences and may support individual level screening of depression. Methods: In this pilot study (n = 84) we collected two longitudinal sessions of behavioural assessment data in a laboratory setting. Depression was assessed using Beck Depression Inventory II (BDI-II), to explore optimal screening methods with machine-learning, and to establish the validity of adapting a novel behavioural assessment focusing on self and emotions for depression screening. Results: The best machine-learning model achieved high performance in depression screening, 10-Fold cross-validation (CV) Area Under the receiver operating characteristic Curve (AUC) of 0.90 and balanced accuracy of 0.81, using a Gradient Boosting algorithm. Prospective prediction using a model trained with session 1 data to predict session 2 depression status achieved a 10-Fold CV AUC of 0.77 and balanced accuracy of 0.66. We also identified interpretable behavioural signatures for depression patients based on the best model. Conclusion: The study supports the utility of using behavioural data as a viable and cost-effective solution for depression screening, with a potential wide range of applications in clinical settings.</p

Grassroots Training for Reproducible Science:A Consortium-Based Approach to the Empirical Dissertation

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