E T Bullmore

In Praise of Tedious Permutation

Tests of the null hypothesis by repeated permutation of the observed data are brutally simple, valid on the basis of only a few assumptions, and adaptable to any test statistic of interest. The history of permutation tests is briefly reviewed, from the pioneering work of R.A. Fisher in the 1930s, to contemporary applications to human brain mapping by several independent groups. Permutation tests for a difference between two sets of brain images at voxel and cluster levels are described, and compared wherever possible to the corresponding theoretical tests. It is shown that nominal Type I error control by permutation is generally excellent; and that some interesting statistics, such as the “mass” of a suprathreshold voxel cluster, are more accessible to testing by permutation than theory. Some limitations of permutation tests are discussed. On balance, the case for permutation tests of the null hypothesis in brain mapping is strong.

Adolescent friendships predict later resilient functioning across psychosocial domains in a healthy community cohort

Background Adolescence is a key time period for the emergence of psychosocial and mental health difficulties. To promote adolescent adaptive (‘resilient’) psychosocial functioning (PSF), appropriate conceptualisation and quantification of such functioning and its predictors is a crucial first step. Here, we quantify resilient functioning as the degree to which an individual functions better or worse than expected given their self-reported childhood family experiences, and relate this to adolescent family and friendship support. Method We used Principal Component and regression analyses to investigate the relationship between childhood family experiences and PSF (psychiatric symptomatology, personality traits and mental wellbeing) in healthy adolescents (the Neuroscience in Psychiatry Network; N = 2389; ages 14–24). Residuals from the relation between childhood family experiences and PSF reflect resilient functioning; the degree to which an individual is functioning better, or worse, than expected given their childhood family experiences. Next, we relate family and friendship support with resilient functioning both cross-sectionally and 1 year later. Results Friendship and family support were positive predictors of immediate resilient PSF, with friendship support being the strongest predictor. However, whereas friendship support was a significant positive predictor of later resilient functioning, family support had a negative relationship with later resilient PSF. Conclusions We show that friendship support, but not family support, is an important positive predictor of both immediate and later resilient PSF in adolescence and early adulthood. Interventions that promote the skills needed to acquire and sustain adolescent friendships may be crucial in increasing adolescent resilient PSF.

Repeated exposure to systemic inflammation and risk of new depressive symptoms among older adults

Evidence on systemic inflammation as a risk factor for future depression is inconsistent, possibly due to a lack of regard for persistency of exposure. We examined whether being inflamed on multiple occasions increases risk of new depressive symptoms using prospective data from a population-based sample of adults aged 50 years or older (the English Longitudinal Study of Ageing). Participants with less than four of eight depressive symptoms in 2004/05 and 2008/09 based on the Eight-item Centre for Epidemiologic Studies Depression scale were analysed. The number of occasions with C-reactive protein ⩾3u2009mgu2009l−1 over the same initial assessments (1 vs 0 occasion, and 2 vs 0 occasions) was examined in relation to change in depressive symptoms between 2008/09 and 2012/13 and odds of developing depressive symptomology (having more than or equal to four of eight symptoms) in 2012/13. In multivariable-adjusted regression models (n=2068), participants who were inflamed on 1 vs 0 occasion showed no increase in depressive symptoms nor raised odds of developing depressive symptomology; those inflamed on 2 vs 0 occasions showed a 0.10 (95% confidence intervals (CIs)=−0.07, 0.28) symptom increase and 1.60 (95% CI=1.00, 2.55) times higher odds. In further analyses, 2 vs 0 occasions of inflammation were associated with increased odds of developing depressive symptoms among women (odds ratio (OR)=2.75, 95% CI=1.53, 4.95), but not among men (OR=0.70, 95% CI=0.29, 1.68); P-for-sex interaction=0.035. In this cohort study of older adults, repeated but not transient exposure to systemic inflammation was associated with increased risk of future depressive symptoms among women; this subgroup finding requires confirmation of validity.

Data supporting NSPN publication 'Mutualistic coupling between vocabulary and reasoning supports cognitive development during late adolescence and early adulthood'

The repository includes two .Rdata files, Cognitivedata.Rdata and fulldemos.Rdata, and a codefile, NSPNAnalysis_full.R. To recreate the analysis, download a copy of free software R, save the .Rdata file in a working directory, change the current working directory within R, and run the analyses.

Data supporting NSPN publication "The NSPN 2400 Cohort: a developmental sample supporting the Wellcome Trust NeuroScience in Psychiatry Network"

Data supporting this publication can be found in the Kiddle_dataset.csv file. A brief description of the variables can be found in Kiddle_dataset_dictionary.txt.

An fMRI study of cognitive activation deficits in symptom-matched first episode and chronic schizophrenia patients

To determine whether abnormal patterns of cerebral activation previously detected in chronic schizophrenia are also present in the first episode, functional magnetic resonance imaging (fMRI) was used to compare brain function in first episode and chronic schizophrenia during a verbal working memory task. Six male, right-handed first episode schizophrenic patients were matched to chronic patients on PANSS scores. One first episode patient was antipsychotic naive; all others were receiving conventional antipsychotics. There was no significant difference in mean daily dose of chlorpromazine equivalents. Two age-matched control groups were used. There was no significant difference between any of the four groups on estimated premorbid IQ. All subjects underwent fMRI while performing a verbal working memory task (the two-back task) incorporating a periodic design. An analysis of variance (p , .01) on a voxel-wise basis was used to compare the first episode group (controls-patients) and the chronic group (controlspatients). The only significant difference in task performance between the four groups was in reaction time during the two back task: Both patient groups had reaction times slower than their respective controls (p , .05). There was no significant difference in activation pattern between the first episode group (controls-patients) and the chronic group (controls-patients). Abnormal patterns of cerebral activation in first episode schizophrenia are similar to those in chronic schizophrenia. Previously detected abnormalities in chronic schizophrenia cannot therefore be solely ascribed to psychosis symptomatology, long-term exposure to antipsychotics, or to post-onset disease progression.

165. An fMRI study of cognitive activation deficits in symptom-matched first episode and chronic schizophrenia patients

To determine whether abnormal patterns of cerebral activation previously detected in chronic schizophrenia are also present in the first episode, functional magnetic resonance imaging (fMRI) was used to compare brain function in first episode and chronic schizophrenia during a verbal working memory task. Six male, right-handed first episode schizophrenic patients were matched to chronic patients on PANSS scores. One first episode patient was antipsychotic naive; all others were receiving conventional antipsychotics. There was no significant difference in mean daily dose of chlorpromazine equivalents. Two age-matched control groups were used. There was no significant difference between any of the four groups on estimated premorbid IQ. All subjects underwent fMRI while performing a verbal working memory task (the two-back task) incorporating a periodic design. An analysis of variance (p , .01) on a voxel-wise basis was used to compare the first episode group (controls-patients) and the chronic group (controlspatients). The only significant difference in task performance between the four groups was in reaction time during the two back task: Both patient groups had reaction times slower than their respective controls (p , .05). There was no significant difference in activation pattern between the first episode group (controls-patients) and the chronic group (controls-patients). Abnormal patterns of cerebral activation in first episode schizophrenia are similar to those in chronic schizophrenia. Previously detected abnormalities in chronic schizophrenia cannot therefore be solely ascribed to psychosis symptomatology, long-term exposure to antipsychotics, or to post-onset disease progression.