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Characterizing a psychiatric symptom dimension related to
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Research article Human biology and medicine Neuroscience. eLife digest When an individual resists the temptation to stay out late in order to get a good. night s sleep he or she is exercising what is known as goal directed control This kind of control. allows individuals to regulate their behaviour in a deliberate manner It is thought that a reduction in. goal directed control may be linked to compulsiveness or compulsivity a psychological trait that. involves excessive repetition of thoughts or actions Furthermore evidence shows that goal directed. control is reduced in people with compulsive disorders such as obsessive compulsive disorder or. OCD and drug addiction However failures of goal directed control have also been reported in. other mental health conditions that are not linked to compulsivity such as social anxiety disorder. The fact that reduced goal directed control is found across various mental health conditions. highlights a core issue in modern psychiatric research and treatment Mental health conditions are. typically defined and diagnosed by their clinical symptoms not by their underlying psychological. traits or biological abnormalities This makes it difficult to determine the cause of a specific disorder. as its symptoms are often rooted in the same psychological and biological traits seen in other. mental health conditions, To start to tackle this issue Gillan et al used a strategy that allowed them to look at compulsivity. as a trans diagnostic dimension that is as something that exists on a spectrum and is not specific. to one disorder but involved in numerous different mental health conditions Nearly 2 000 people. completed an online task that assessed goal directed control and filled in questionnaires that. measured symptoms of various mental health conditions Gillan et al showed that as expected. people with reduced goal directed control were generally more compulsive and that this. relationship could be seen in the context of both OCD and other compulsive disorders such as. Further by leveraging the efficiency of online data collection to collect such a large sample. Gillan et al were also able to examine how much different symptoms co occurred in people This. enabled them to use a statistical technique to pick out three trans diagnostic dimensions. compulsive behaviour and intrusive thought anxious depression and social withdrawal and found. that only the compulsive factor was associated with reduced goal directed control In fact reduced. goal directed control was found to be more closely related to compulsivity than the symptoms of. traditional mental health disorders including OCD These findings show that research into the causes. of mental health conditions and perhaps ultimately diagnosis and treatment all of which have. traditionally approached specific disorders in isolation would benefit greatly from a trans. diagnostic approach,DOI 10 7554 eLife 11305 002, our habits organisms are capable of goal directed behavior This refers our ability to make more. considered choices reflecting both i knowledge of the outcomes that our actions typically produce. and ii our current motivation for those outcomes Dickinson and Balleine 1994 Consistent with. the hypothesis that compulsion is linked to an imbalance between these modes of control deficits in. goal directed learning have been observed across a range of putatively compulsive disorders such. as drug addiction Sjoerds et al 2013 Voon et al 2015 obsessive compulsive disorder OCD. Voon et al 2015 Gillan et al 2011 2014a 2014b 2015a and also binge eating disorder. Voon et al 2015 These deficits in goal directed control have been linked to abnormal structure. and function of the caudate and medial orbitofrontal cortex Voon et al 2015 Gillan et al. 2015a suggesting that they may be a promising target for understanding the etiology of these dis. orders and thus for future treatment development, Critically the scope of the relationship between goal directed learning deficits and psychopathol. ogy and particularly their specificity to compulsive versus non compulsive aspects has not been. established In fact a similar deficit in goal directed control was recently reported in other patient. groups Alvares et al 2014 Morris et al 2015 including those diagnosed with social anxiety dis. order and schizophrenia at least the former of which is not characterized by repetitive compulsive. acts This casts serious doubt over the hypothesis that goal directed deficits are a neurocognitive. mechanism that is partly responsible for psychiatric compulsivity This lack of specificity is. Gillan et al eLife 2016 5 e11305 DOI 10 7554 eLife 11305 2 of 24. Research article Human biology and medicine Neuroscience. unfortunately ubiquitous in psychiatry research Lipszyc and Schachar 2010 Bickel et al 2012 a. result we suggest of the broader issue that psychiatric diagnostic categories do not reflect the. most discrete and neurobiologically informative phenomena Of particular relevance to the present. study are the high rates of co morbidity between OCD and social anxiety disorder Ruscio et al. 2010 the preponderance of OCD symptoms in the schizophrenia poopulation Poyurovsky and. Koran 2005 and more broadly that the vast majority of patients diagnosed with obsessive compul. sive disorder OCD meet the criteria for another lifetime psychiatric disorder Ruscio et al 2010. Given these major overlaps dissociating the neurocognitive bases for these respective diagnostic. categories in their current form may be untenable, Indeed the Diagnostic and Statistical Manual of Mental Disorders DSM now in it s fifth edition. American Psychiatric Association 2013 was developed to provide a reliable descriptive psychiat. ric taxonomy rather than an etiologically valid one As such it is difficult to clearly discriminate the. diagnostic categories it defines on the basis of genetics neuroimaging or indeed any of the modern. tools of cognitive neuroscience These issues have been described in detail by others Cuthbert and. Kozak 2013 Hyman 2007 Robbins et al 2012 and have been recognized by the National Insti. tute of Mental Health NIMH which has launched the Research Domain Criteria RDoC initiative. aiming to identify biologically plausible trans diagnostic markers of psychiatric disturbances. Insel et al 2010 Although progress towards this goal has already been made by studies examin. ing dissociable clusters of patients within groups diagnosed with the same disorder. Brodersen et al 2014 Fair et al 2012 the identification of robust generalizable and specific. markers that contribute to psychiatric co morbidity has been curtailed by the small sample sizes that. are typical of patient studies, Accordingly we hypothesized that a dimensional approach leveraging the efficiencies of large.
scale online data collection among healthy individuals could be used to determine the precise psy. chiatric phenotype associated with deficits in goal directed control and test the specificity of this. relationship with respect to other aspects of psychopathology We hypothesized that this phenotype. would broadly relate to compulsive behavior which is seen across multiple disorders including OCD. and addiction Gillan et al 2015b but were interested to reveal the scope and generality of this. e g with respect to impulsivity a putatively related clinical phenotype Robbins et al 2012 We. also wished to study how any psychiatric correlates of goal directed control relate to variation in age. and IQ two more general factors that have been shown to covary both with goal directed control. and with some aspects of psychopathology Eppinger et al 2013 Schad et al 2014. Sandstrom et al 1998 To this end rather than diagnosed patients we used two large general. population samples collected online via Amazon s Mechanical Turk AMT to test i if compulsivity as. indicated by self report OCD symptoms is associated with individual differences in goal directed. learning ii if this association generalizes to self report symptoms of other DSM diagnostic catego. ries that involve compulsivity and iii if this association is specific to compulsive versus non compul. sive psychopathology, Goal directed control has recently been computationally formalized as arising from a form of rein. forcement learning known as model based Daw et al 2011 which can be expressed as an indi. vidual difference measure that has been shown to predict how likely individuals are to form habits. Gillan et al 2015c Using this well validated task Figure 1 Daw et al 2011 we found support. for all three postulates In Experiment 1 we found that total scores on a self report questionnaire. measuring the severity of OCD symptoms were tracked by normal variation in model based learning. in the general population but not by self report anxiety or depression symptoms In Experiment 2. we replicated the association with self report OCD symptoms and showed that it generalized to a. broader set of psychiatric symptoms that similarly involve failures in exerting control over self delete. rious behaviors specifically alcohol addiction eating disorders and impulsivity Once again we. found tentative evidence for specificity with respect to non compulsive aspects of psychopathology. Next we conducted a factor analysis which indicated the existence of three latent symptom dimen. sions that cut across the nine different questionnaires assessed in this study Crucially the second. symptom dimension identified was characterized by Compulsive Behavior and Intrusive Thought in. which items were most consistently drawn from the questionnaires assessing symptoms of OCD eat. ing disorders and addiction pertaining not just to repetitive compulsive behaviors as was our pre. diction but also to associated preoccupations and cognitive distortions This factor which was. defined independently of task performance was a significant predictor of deficits in model based. Gillan et al eLife 2016 5 e11305 DOI 10 7554 eLife 11305 3 of 24. Research article Human biology and medicine Neuroscience. Figure 1 Two step reinforcement learning task used to assess goal directed model based learning a Subjects chose between two fractals which. probabilistically determined whether they would transition to the orange or blue second stage state For example the fractal on the left had a 70. chance of leading to the blue second stage state common transition and a 30 chance of leading to the orange state rare transition These. transition probabilities were fixed and could be learned over time In the second stage state subjects chose between two fractals each of which was. associated with a distinct probability of being rewarded with a 25 cents coin The probability of receiving a reward associated with each second stage. fractal could also be learned but unlike the transition structure these drifted slowly over time 0 25 P 0 75 panel b This meant that in order to. earn the most rewards possible subjects had to track which second stage fractals were currently best as they changed over time Reward probabilities. depicted 34 68 72 67 refer to example trial 50 denoted by the vertical dashed line in b b Drifting reward probabilities determined by. Gaussian Random Walks for 200 trials with grey horizontal lines indicating boundaries at 0 25 and 0 75 c Schematic representing the performance of a. purely model free learner who only exhibits sensitivity to whether or not the previous trial was rewarded vs unrewarded and does not modify their. behavior in light of the transition that preceded reward d Schematic representing the performance of a purely model based learner who is more. likely to repeat an action i e stay following a rewarded trial only if the transition was common If the transition to that rewarded state was rare they. are more likely to switch on the next trial,DOI 10 7554 eLife 11305 003. learning Crucially this effect was highly specific to this factor when directly compared to the two. other factors identified in this analysis Anxious Depression and Social Withdrawal. In Experiment 1 we tested the hypothesis that individual differences in total scores on a question. naire assessing the severity of OCD symptoms are associated with normal variation in goal directed. control rather than necessitating the categorical comparison of OCD patient vs control groups Par. ticipants N 548 first completed a reinforcement learning task that quantifies individual differences. in goal directed model based learning which is operationalized as a parameter estimate from a. logistic regression analysis predicting choices in the task see Materials and methods and refs. Daw et al 2011 Gillan et al 2015c Next we administered a short Intelligence Quotient IQ. Gillan et al eLife 2016 5 e11305 DOI 10 7554 eLife 11305 4 of 24. Research article Human biology and medicine Neuroscience. test followed by self report questionnaires assessing symptoms of OCD along with depression and. trait anxiety which we did not expect to be associated with goal directed deficits In line with our. hypothesis there was a significant association between scores on the OCD questionnaire and goal. directed deficits i e a negative relationship between OCD severity and model based learning b. 0 040 Standard Error SE 0 02 p 0 049 when as in all analyses reported henceforth control. ling for age IQ and gender which have been previously reported to covary with goal directed. behavior Eppinger et al 2013 Schad et al 2014 Sandstrom et al 1998 Specifically for. Research article Human biology and medicine Neuroscience unfortunately ubiquitous in psychiatry research Lipszyc and Schachar 2010 Bickel et al 2012 a result we suggest of the broader issue that psychiatric diagnostic categories do not reflect the

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