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The present paper presents a fundamentally novel approach to model individual differences of persons with the same biologically heterogeneous mental disorder. Unlike prevalent case-control analyses, that assume a clear distinction between patient and control groups and thereby introducing the concept of an ‘average patient’, we describe each patient's biology individually, gaining insights into the different facets that characterize persistent attention-deficit/hyperactivity disorder (ADHD).
Using a normative modeling approach, we mapped inter-individual differences in reference to normative structural brain changes across the lifespan to examine the degree to which case-control analyses disguise differences between individuals.
At the level of the individual, deviations from the normative model were frequent in persistent ADHD. However, the overlap of more than 2% between participants with ADHD was only observed in few brain loci. On average, participants with ADHD showed significantly reduced gray matter in the cerebellum and hippocampus compared to healthy individuals. While the case-control differences were in line with the literature on ADHD, individuals with ADHD only marginally reflected these group differences.
Case-control comparisons, disguise inter-individual differences in brain biology in individuals with persistent ADHD. The present results show that the ‘average ADHD patient’ has limited informative value, providing the first evidence for the necessity to explore different biological facets of ADHD at the level of the individual and practical means to achieve this end.
A diagnosis of dissociative identity disorder (DID) is controversial and prone to under- and misdiagnosis. From the moment of seeking treatment for symptoms to the time of an accurate diagnosis of DID individuals received an average of four prior other diagnoses and spent 7 years, with reports of up to 12 years, in mental health services.
To investigate whether data-driven pattern recognition methodologies applied to structural brain images can provide biomarkers to aid DID diagnosis.
Structural brain images of 75 participants were included: 32 female individuals with DID and 43 matched healthy controls. Individuals with DID were recruited from psychiatry and psychotherapy out-patient clinics. Probabilistic pattern classifiers were trained to discriminate cohorts based on measures of brain morphology.
The pattern classifiers were able to accurately discriminate between individuals with DID and healthy controls with high sensitivity (72%) and specificity (74%) on the basis of brain structure. These findings provide evidence for a biological basis for distinguishing between DID-affected and healthy individuals.
We propose a pattern of neuroimaging biomarkers that could be used to inform the identification of individuals with DID from healthy controls at the individual level. This is important and clinically relevant because the DID diagnosis is controversial and individuals with DID are often misdiagnosed. Ultimately, the application of pattern recognition methodologies could prevent unnecessary suffering of individuals with DID because of an earlier accurate diagnosis, which will facilitate faster and targeted interventions.
Declaration of interest
The authors declare no competing financial interests.
Differentiating bipolar from recurrent unipolar depression is a major clinical challenge. In 18 healthy females and 36 females in a depressive episode – 18 with bipolar disorder type I, 18 with recurrent unipolar depression – we applied pattern recognition analysis using subdivisions of anterior cingulate cortex (ACC) blood flow at rest, measured with arterial spin labelling. Subgenual ACC blood flow classified unipolar v. bipolar depression with 81% accuracy (83% sensitivity, 78% specificity).
Bipolar disorder (BD) is one of the leading causes of disability worldwide. Patients are further disadvantaged by delays in accurate diagnosis ranging between 5 and 10 years. We applied Gaussian process classifiers (GPCs) to structural magnetic resonance imaging (sMRI) data to evaluate the feasibility of using pattern recognition techniques for the diagnostic classification of patients with BD.
GPCs were applied to gray (GM) and white matter (WM) sMRI data derived from two independent samples of patients with BD (cohort 1: n = 26; cohort 2: n = 14). Within each cohort patients were matched on age, sex and IQ to an equal number of healthy controls.
The diagnostic accuracy of the GPC for GM was 73% in cohort 1 and 72% in cohort 2; the sensitivity and specificity of the GM classification were respectively 69% and 77% in cohort 1 and 64% and 99% in cohort 2. The diagnostic accuracy of the GPC for WM was 69% in cohort 1 and 78% in cohort 2; the sensitivity and specificity of the WM classification were both 69% in cohort 1 and 71% and 86% respectively in cohort 2. In both samples, GM and WM clusters discriminating between patients and controls were localized within cortical and subcortical structures implicated in BD.
Our results demonstrate the predictive value of neuroanatomical data in discriminating patients with BD from healthy individuals. The overlap between discriminative networks and regions implicated in the pathophysiology of BD supports the biological plausibility of the classifiers.
At present there are no objective, biological markers that can be used to reliably identify individuals with post-traumatic stress disorder (PTSD). This study assessed the diagnostic potential of structural magnetic resonance imaging (sMRI) for identifying trauma-exposed individuals with and without PTSD.
sMRI scans were acquired from 50 survivors of the Sichuan earthquake of 2008 who had developed PTSD, 50 survivors who had not developed PTSD and 40 healthy controls who had not been exposed to the earthquake. Support vector machine (SVM), a multivariate pattern recognition technique, was used to develop an algorithm that distinguished between the three groups at an individual level. The accuracy of the algorithm and its statistical significance were estimated using leave-one-out cross-validation and permutation testing.
When survivors with PTSD were compared against healthy controls, both grey and white matter allowed discrimination with an accuracy of 91% (p < 0.001). When survivors without PTSD were compared against healthy controls, the two groups could be discriminated with accuracies of 76% (p < 0.001) and 85% (p < 0.001) based on grey and white matter, respectively. Finally, when survivors with and without PTSD were compared directly, grey matter allowed discrimination with an accuracy of 67% (p < 0.001); in contrast the two groups could not be distinguished based on white matter.
These results reveal patterns of neuroanatomical alterations that could be used to inform the identification of trauma survivors with and without PTSD at the individual level, and provide preliminary support to the development of SVM as a clinically useful diagnostic aid.
Group-level results suggest that relative to healthy controls (HCs), ultra-high-risk (UHR) and first-episode psychosis (FEP) subjects show alterations in neuroanatomy, neurofunction and cognition that may be mediated genetically. It is unclear, however, whether these groups can be differentiated at single-subject level, for instance using the machine learning analysis support vector machine (SVM). Here, we used a multimodal approach to examine the ability of structural magnetic resonance imaging (sMRI), functional MRI (fMRI), diffusion tensor neuroimaging (DTI), genetic and cognitive data to differentiate between UHR, FEP and HC subjects at the single-subject level using SVM.
Three age- and gender-matched SVM paired comparison groups were created comprising 19, 19 and 15 subject pairs for FEP versus HC, UHR versus HC and FEP versus UHR, respectively. Genetic, sMRI, DTI, fMRI and cognitive data were obtained for each participant and the ability of each to discriminate subjects at the individual level in conjunction with SVM was tested.
Successful classification accuracies (p < 0.05) comprised FEP versus HC (genotype, 67.86%; DTI, 65.79%; fMRI, 65.79% and 68.42%; cognitive data, 73.69%), UHR versus HC (sMRI, 68.42%; DTI, 65.79%), and FEP versus UHR (sMRI, 76.67%; fMRI, 73.33%; cognitive data, 66.67%).
The results suggest that FEP subjects are identifiable at the individual level using a range of biological and cognitive measures. Comparatively, only sMRI and DTI allowed discrimination of UHR from HC subjects. For the first time FEP and UHR subjects have been shown to be directly differentiable at the single-subject level using cognitive, sMRI and fMRI data. Preliminarily, the results support clinical development of SVM to help inform identification of FEP and UHR subjects, though future work is needed to provide enhanced levels of accuracy.
The human race, to which so many of my readers belong, has been playing at children's games from the beginning… [O]ne of the games to which it most attached is called… ‘Cheat the Prophet’. [The prophets] took something or other that was certainly going on in their time, and then said it would go on more and more until something extraordinary happened. … The players listen very carefully and respectfully to all that the clever men have to say about what is to happen in the next generation. The players then wait until all the clever men are dead, and bury them nicely. They then go and do something else.
(G. K. Chesterton, The Napoleon of Notting Hill)
In part it is due to a genuine misunderstanding of the philosophical implications of the natural sciences, the great prestige of which has been misappropriated by many a fool and imposter since their earliest triumphs. But principally it seems to me to spring from a desire to resign our responsibility, to cease from judging provided we be not judged ourselves and, above all, are not compelled to judge ourselves – from a desire to flee for refuge to some vast, amoral, impersonal, monolithic whole – nature, or history, or class, or race, or the irresistible evolution of the social structure … which it is senseless to evaluate or criticise, and which we resist to our certain doom. […]
The human race, to which so many of my readers belong, has been playing at children's games from the beginning… [O]ne of the games to which it most attached is called… ‘Cheat the Prophet’. [The prophets] took something or other that was certainly going on in their time, and than sait it would go on more and more until something extraordinary happened. … The players listen very carefully and respectfully to all that the clever men have to say about what is to happen in the next generation. The players then wait until att the clever men are dead, and bury them nicely. They then go and do something else.
‘I have changed everything’, Mrs Thatcher is supposed to have said in 1976. For long her claim was taken at face value, by outraged opponents no less than by eager supporters. Her fall, and the misadventures of her successor, have brought a new perspective. Post-Thatcher Britain is beginning to look suspiciously like pre-Thatcher Britain; the supposedly transformed state of the revolutionaries like the unregenerate state of the ancien régime. In this essay, I explore the possible reason for this curious state of affairs. I suggest that its origins may lie in the hold on the imaginations of the British political class of three competing visions of the British state, all of which have deep roots in British history, but all of which have been emptied by the upheavals of the last twenty years or so. I conclude with the hope – for it is only a hope – that a fourth and more promising vision, equally venerable, but in this century less influential, may replace them. The ‘twilight’ of my title is, in short, intended to be a warning, not a prediction. Twilight certainly lies in wait for states that cannot adapt to the momentous changes now taking place in civil society and in the international economy. Some spectacular examples have occurred quite recently. And there is no divine law exempting the British state from the need to adapt. But it is up to us to decide whether we do so or no.
The visions exhibited
I begin, like a barrister introducing a case, with three exhibits.
The Relationship between the market and the forum, between exchange and persuasion, between the public realm of the citizen and the private realm of the consumer, has been a central preoccupation of social thought since the days of Aristotle. For most of the post-war period, however, and in most western countries, the tensions inherent in that relationship appeared to have been resolved. Then came the ‘stagflation’ of the 1970s, the rise of the New Right, the associated rebirth of economic liberalism and a variety of more or less successful attempts to clip the wings of the post-war welfare state. Classic questions, which the post-war generation imagined it had answered, returned to the agenda—among them the questions of what citizenship means in a market economy, and of how the promise of citizenship is to be realised in complex modern societies. These questions are of significance to all advanced societies, of course; as the most cursory reading of Vaclav Havel's essays shows, they resonate with particular force in eastern Europe. Perhaps because she has been the chief European testing ground for New Right theory, however, they have also begun to resonate with unusual power in Britain; and it is plausible to imagine that the British case may be more relevant to the rest of the western world than are the various East European cases. Hence, this essay. It begins by looking at the British debate and the factors which have given rise to it, and then tries to clarify some of the issues it poses.
TRIADS ARE IN FASHION. IN POLITICS AND MARKETS, Charles Lindblom distinguishes between three kinds of social relationships — the exchange relations characteristic of markets; the authority relations characteristic of states; and what he calls ‘preceptoral’ relations, the relations of teachers to pupils, of advertisers to consumers, of indoctrinators to the indoctrinated. In the epilogue to The Liberal Theory of Justice, Brian Barry proposes a different, but in some respects complementary, triad. There are, he suggests, three ‘models’ of social collaboration.
IT IS A COMMONPLACE THAT BRITISH POLITICS ARE AT PRESENT less consensual, and more polarized ideologically, than they have been for a generation. It is also a commonplace that the ideological polarization of the 1980s has its roots in the economic and political failures of the 1960s and 1970s.
WHATEVER MAY BE IN DOUBT ABOUT THE CURRENT CRISIS IN the Labour Party, one thing is clear. In a sense true of no other internal crisis in the 62 years since the loose and inchoate ‘Labour Alliance’ of 1900 first became a true political party, with individual members and a distinctive claim to power, the arguments which have provoked it concern the rules of the game as well as moves within the game: the way in which party decisions are made and enforced, as well as the content of the decisions themselves. This, of course, is why the arguments are so fierce and the crisis so deep. Policy defeats can be revised later if Fortune's wheel turns again. Constitutional defeats damage the losers permanently. It is true, no doubt, that both sides in the current struggle have exaggerated the likely consequences of the changes forced through at the October party conference. The old French saying that there is more in common between two deputies, one of whom is a Communist, than between two Communists, one of whom is a deputy has not suddenly lost all relevance to Westminster merely because Labour MPs will have to face compulsory reselection between general elections, or because the party leader is elected in an electoral college. Reselection will not re-make the Parliamentary Labour Party in the image of constituency management committees, and the creation of an electoral college will not free the leader from the need to win and hold the confidence of his parliamentary colleagues. When all the necessary qualifications have been made, however, there can be no doubt that the constitutional changes will shift the balance of party power to the advantage of the Left and to the detriment of the Right — as, of course, they were intended to do. That is what the struggle has been about; and the media have been right to concentrate their attention on that aspect of it.
THE LABOUR PARTY WAS DECISIVELY DEFEATED AT THE 1979 general election. The Conservatives not only won 70 more seats than Labour but its lead of 6.9% was considerably bigger than that of Harold Macmdlan in 1959, while the swing away from Labour to Tory was the largest since 1945. What is even more depressing is that the Labour share of the poll was its lowest since 1931.