Original Investigation | Psychiatry

Association of Environmental Uncertainty With Altered Decision-making

and Learning Mechanisms in Youths With Obsessive-Compulsive Disorder
Aleya A. Marzuki, PhD; Ivan Tomić, PhD; Samantha Hiu Yan Ip, PhD; Julia Gottwald, PhD; Jonathan W. Kanen, PhD; Muzaffer Kaser, MD, PhD; Akeem Sule, MD;
Anna Conway-Morris, MD; Barbara J. Sahakian, DSc; Trevor W. Robbins, PhD

Abstract Key Points

Question Is decision-making associated
IMPORTANCE Adults with obsessive-compulsive disorder (OCD) display perseverative behavior in
with environmental uncertainty in
stable environments but exhibit vacillating choice when payoffs are uncertain. These findings may be
youths with obsessive-compulsive
associated with intolerance of uncertainty and compulsive behaviors; however, little is known about
disorder (OCD)?
the mechanisms underlying learning and decision-making in youths with OCD because research into
this population has been limited. Findings In this cross-sectional study of
103 individuals, hierarchical
OBJECTIVE To investigate cognitive mechanisms associated with decision-making in youths with reinforcement learning models fitted to
OCD by using executive functioning tasks and computational modeling. 2 clinical data sets indicated that youths
12 to 19 years of age with OCD revealed
DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, 50 youths with OCD atypical trial-by-trial performance on a
(patients) and 53 healthy participants (controls) completed a probabilistic reversal learning (PRL) probabilistic reversal learning 2-choice
task between January 2014 and March 2020. A separate sample of 27 patients and 46 controls task. However, on a deterministic
completed the Wisconsin Card Sorting Task (WCST) between January 2018 and November 2020. set-shifting task, youths with OCD did
The study took place at the University of Cambridge in the UK. not show marked differences from
healthy controls.
MAIN OUTCOMES AND MEASURES Decision-making mechanisms were studied by fitting
Meaning Obsessive-compulsive
hierarchical bayesian reinforcement learning models to the 2 data sets and comparing model
disorder in youths was associated with
parameters between participant groups. Model parameters included reward and punishment
impaired decision-making during
learning rates (feedback sensitivity), reinforcement sensitivity and decision consistency
probabilistic tasks but not deterministic
(exploitation), and stickiness (perseveration). Associations of receipt of serotonergic medication with
tasks, contributing to growing evidence
performance were assessed.
that youths with OCD may have
difficulty coping with environmental
RESULTS In total, 50 patients (29 female patients [58%]; median age, 16.6 years [IQR, 15.3-18.0
uncertainty.
years]) and 53 controls (30 female participants [57%]; median age, 16.4 years [IQR, 14.8-18.0 years])
completed the PRL task. A total of 27 patients (18 female patients [67%]; median age, 16.1 years [IQR,
15.2-17.2 years]) and 46 controls (28 female participants [61%]; median age, 17.2 [IQR, 16.3-17.6 + Supplemental content
years]) completed the WCST. During the reversal phase of the PRL task, patients made fewer correct Author affiliations and article information are
responses (mean [SD] proportion: 0.83 [0.16] for controls and 0.61 [0.31] for patients; 95% CI, −1.31 listed at the end of this article.

to −0.64) and switched choices more often following false-negative feedback (mean [SD]
proportion: 0.09 [0.16] for controls vs 0.27 [0.34] for patients; 95% CI, 0.60-1.26) and true-positive
feedback (mean [SD] proportion: 0.93 [0.17] for controls vs 0.73 [0.34] for patients; 95% CI, −2.17
to −1.31). Computational modeling revealed that patients displayed enhanced reward learning rates
(mean difference [MD], 0.21; 95% highest density interval [HDI], 0.04-0.38) but decreased
punishment learning rates (MD, −0.29; 95% HDI, −0.39 to −0.18), reinforcement sensitivity (MD,
−4.91; 95% HDI, −9.38 to −1.12), and stickiness (MD, −0.35; 95% HDI, −0.57 to −0.11) compared with
controls. There were no group differences on standard WCST measures and computational model
parameters. However, patients who received serotonergic medication showed slower response
times (mean [SD], 1420.49 [279.71] milliseconds for controls, 1471.42 [212.81] milliseconds for

(continued)

Open Access. This is an open access article distributed under the terms of the CC-BY License.

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Abstract (continued)

patients who were unmedicated, and 1738.25 [349.23] milliseconds for patients who were
medicated) (control vs medicated MD, −320.26 [95% CI, −547.00 to −88.68]) and increased unique
errors (mean [SD] proportion: 0.001 [0.004] for controls, 0.002 [0.004] for patients who were
unmedicated, and 0.008 [0.01] for patients who were medicated) (control vs medicated MD,
−0.007 [95% CI, −3.14 to −0.36]) on the WCST.

CONCLUSIONS AND RELEVANCE The results of this cross-sectional study indicated that youths
with OCD showed atypical probabilistic reversal learning but were generally unimpaired on the
deterministic WCST, although unexpected results were observed for patients receiving serotonergic
medication. These findings have implications for reframing the understanding of early-onset OCD
as a disorder in which decision-making is associated with uncertainty in the environment, a potential
target for therapeutic treatment. These results provide continuity with findings in adults with OCD.

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Corrected on December 29, 2021. doi:10.1001/jamanetworkopen.2021.36195

Introduction
Obsessive-compulsive disorder (OCD) in adults is characterized by widespread cognitive
dysfunction, particularly in domains of cognitive flexibility and response inhibition.1,2 Difficulties in
shifting attention from ingrained thoughts and actions (inflexibility) and inhibiting inappropriate
responses (response disinhibition) are thought to promote uncontrollable obsessions and urges.
Curiously, evidence for these cognitive biomarkers in adolescent and child patients with OCD is
sparse.3,4 Hence, it is now necessary to identify a cognitive biomarker that can better account for
both pediatric- and adult-OCD symptomatology.
Cognition among individuals with OCD may be altered as a function of task stochasticity (ie,
whether task outcomes have certain or uncertain payoffs). On deterministic set-shifting tasks, such
as the Wisconsin Card Sorting Task (WCST), which involves learning from consistently reliable
feedback to choose cards based on a rule (eg, color) and switching behavior when feedback changes
(eg, switching from color to shape), adults with OCD typically commit more perseverative errors than
healthy adults because adults with OCD inappropriately attend to previously correct rules and are
slower to learn new rules.5-11 The inverse is apparent on probabilistic reversal learning (PRL) tasks. On
such tasks, participants must first identify which of 2 stimuli reliably delivers positive feedback (eg,
70% of the time) and repeatedly select the more optimal stimulus on every trial to maximize
rewards. When a criterion or a certain number of trials has been reached, a reversal of reward
probabilities occurs, wherein the previously rewarded stimulus now becomes suboptimal (is now
30% rewarding). Recent computational studies report that adults with OCD show increased choice
switching irrespective of feedback (also known as reduced stimulus stickiness) on PRL tasks.12-14
Thus, the adult OCD literature indicates a stark pattern of inflexibility when tasks are deterministic
but more inconsistent choosing when tasks are probabilistic. However, there is emerging evidence
that adults with OCD also display abnormal choice switching on the WCST.15 Researchers theorize
that this aberrant choice switching is attributed to “overcomplicated exploration,” in which adults
with OCD attempt to evaluate too many rules at once.15
It is unknown whether choice switching extends to young people with OCD. Results from this
population on deterministic set-shifting tasks have been mixed.3 By contrast, contemporary
empirical research reports that youths with OCD are prone to exhibiting poor learning, suboptimal
decision-making, and increased evidence accumulation.16-18 However, studies have not fully
addressed whether task stochasticity impacts decision-making.
Enhanced choice exploration during decision-making in patients with OCD could have clinical
significance, in that the behavior is associated with patients doubting their decisions. These doubts

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may be promoting an inability to commit to a choice, even when evidence accumulated so far reveals
a specific choice to be clearly more advantageous. In daily life, doubt may similarly be driving patient
compulsions, such as checking locks, doors, and appliances.
Prior research probing cognition in pediatric OCD typically used frequentist statistical methods
to analyze data, which may lack the sensitivity necessary to uncover more subtle behavioral
anomalies. Thus, we sought to infer the mechanisms underlying learning and decision-making in
juveniles with OCD by using a computational psychiatry approach. We fitted well-validated
reinforcement learning models to specially acquired WCST and PRL data sets, which enabled us to
investigate components of decision-making (reward and punishment sensitivity, exploration, and
perseveration) that may distinguish adolescents with OCD from neurotypical adolescents. We
hypothesized that youths aged 12 to 19 years with OCD would show reduced perseveration and
increased exploration on the 2 tasks, which is consistent with findings in adults with OCD.
Incidentally, because suitable sample sizes were available, we sought to explore the association of
serotonergic medication with decision-making in patients.

Methods
Participants
This study is reported according to the Strengthening the Reporting of Observational Studies in
Epidemiology (STROBE) guideline and was approved by the East of England–Essex Research Ethics
Committee. All volunteers gave informed written consent that was obtained in a manner consistent
with the East of England–Essex Research Ethics Committee requirements. Parental consent was
obtained for participants younger than 16 years of age. Participants were compensated at the rate of
£8 (approximately US $11) per hour.
Youths with OCD were recruited via Child and Adolescent Mental Health Services throughout
the United Kingdom. Healthy control participants were recruited via advertisements in state
secondary schools and notice boards located in Cambridgeshire. Patients were screened by an
experienced psychiatrist to rule out comorbid psychiatric and neurological conditions. Control
participants were screened to rule out neurological or psychiatric illnesses.
To qualify for the study, youths in the OCD group had to meet Diagnostic and Statistical Manual
of Mental Disorders (Fifth Edition) (DSM-5) diagnostic criteria for OCD. Apart from OCD, other
significant Axis I mental disorders as diagnosed according to DSM-5 criteria were exclusion criteria.
Youths with severe physical impairments affecting eyesight or motor performance were also
excluded because these impairments were hypothesized to affect performance on the tasks.
Participants were aged 12 to 19 years and were fluent in English.
For the WCST, 44 youths with OCD were screened, and 17 were excluded for comorbidities. For
the PRL task, 104 youths with OCD were screened, and 54 were excluded for comorbidities.

Tasks
The WCST and PRL task were administered in person to participants as measures of learning and
flexibility. The WCST was used to assess deterministic learning, and the PRL task probed probabilistic
learning (Figure 1 and eMethods in the Supplement).

Statistical Analysis
The outcome measures for the PRL task were the proportion of perseverative errors, that is, the
number of perseverative responses made in a row immediately following reversal, the proportion of
correct responses (proportion of correct choices), the proportion of switching following spurious
(false) negative feedback, the proportion of staying following veridical (true) positive feedback, and
the mean response times (RTs, in milliseconds). A mixed regression was used to model RT, a binomial
regression was used to model p(perseverative), and mixed binomial regressions were used to model

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the other measures. All mixed regression models were multivariable because they included group
and phase (acquisition and reversal) as independent measures.
The following outcome measures are reported for the WCST: the number of sets completed (out
of 9), proportion of perseverative errors (ie, incorrectly choosing a deck based on the rule from the
previous set), proportion of nonperseverative errors (errors that were not perseverative), proportion
of unique errors (a deck chosen that does not match the test card on any rule), number of set
maintenance failures (number of times participants chose wrongly after establishing the rule),
number of trials needed to complete first set, and RT. All variables were included in multivariate linear
regressions with group as an independent variable, except for proportion of perseverative errors,
proportion of nonperseverative, and proportion of unique errors, which were modeled using
multivariate binomial regressions.
Analyses for both tasks were repeated with z-scored ages, sex, and IQ included as covariates. To
control for multiple comparisons, P values were adjusted according to the Benjamini-Hochberg
procedure.19 Analyses for both tasks were reconducted after subdividing the OCD group into
medicated and unmedicated participants. Post hoc comparisons for control, unmedicated, and
medicated youths were conducted using the emmeans R package,20 with Bonferroni corrections
applied (eMethods in the Supplement).
Data analysis was performed using RStudio, version 4.0.4 (R Foundation for Statistical
Computing). Statistical significance was set at P < .05, and all tests were 2-tailed.

Computational Models
To investigate mechanisms underlying decision-making, we fitted families of hierarchical bayesian
reinforcement learning models to trial-by-trial task data. Models for both tasks were compared using

Figure 1. Wisconsin Card Sorting Task and Probabilistic Reversal Learning Task

A Wisconsin Card Sorting Task B Probabilistic reversal learning task

Use mouse to sort card. +

+
Trial Use mouse to sort card.

start Trial Choice

start
Correct
Use mouse to sort card. Choice made and
Subject Incorrect feedback displayed
chooses deck
+
Stimuli positions
Feedback change

C Reward structure of probabilistic reversal learning task

Acquisition Reversal

Optimal Nonoptimal
80% Correct 20% Correct
20% Incorrect 80% Incorrect

Nonoptimal Optimal
20% Correct 80% Correct
80% Incorrect 20% Incorrect

A, On each trial, participants sort cards appearing at the bottom of the screen into any of
the 4 decks based on a rule (number, color, or shape) and use the feedback given to
discern the rule. The rule changes after 10 cards have been sorted correctly
consecutively. B, On every trial, participants choose between 2 colored stimuli presented
on a screen. Immediately after each choice, they are given feedback. C, During the
acquisition phase (first 40 trials), the stimulus chosen first provides positive feedback
80% of the time, whereas the other stimulus provides positive feedback 20% of the
time. After 40 trials, the reversal phase begins with feedback contingencies associated
with each stimulus reversed.

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a bridge sampling estimate of the marginal likelihood via the bridgesampling R package.21 The best-
fitting model for the PRL data was a reinforcement learning model with 4 free parameters: reward
rate, punishment rate, reinforcement sensitivity, and stickiness.13 The best-fitting WCST model was a
sequential learning model22,23 with 3 free parameters: reward rate, punishment rate, and decision
consistency. Reward and punishment rate parameters in both task models represented how quickly
participants updated their beliefs about the values associated with choices following respective
negative and positive feedback. A high punishment rate signals that a participant learns quickly from
negative feedback, while a high reward rate signifies quicker learning following positive feedback.
The decision consistency parameter from the WCST model and reinforcement sensitivity from the
PRL model both influenced the estimated probability of choosing a specific stimulus per trial. Larger
values of those parameters indicated increased exploitation (a preference for choosing the stimulus
with the higher perceived value), whereas lower values indicated increased exploration (more
random and less value-driven choices). Finally, stickiness (perseveration) in the PRL model described
the extent to which previous choices were repeated irrespective of feedback.
We analyzed differences in parameter values between groups by first calculating group mean
differences (MDs) (posterior distribution of youths in the control group minus posterior distribution
of youths with OCD) per parameter. The 95% and 90% highest density intervals (HDIs)24 of the
posterior distribution per MD were then calculated and inspected to check whether they reliably
included zero (indicating no difference between groups). Full details of model formulation, model-
fitting, and parameter recovery are in the eMethods and eTables 12, 13, 14, and 15 in the Supplement.
We applied Pearson correlations to assess associations between model parameters and clinical
measures (eTables 16, 17, 18, 19, 20, and 21 and eFigures 5 and 6 in the Supplement). We also modeled
data from 20 youths with OCD and 17 control participants who completed both the WCST and PRL
task to draw more direct comparisons on behavior in both tasks (eFigure 7 in the Supplement).

Results
A total of 50 patients with OCD (29 female patients [58%] and 21 male patients [42%]; median age,
16.6 years [IQR, 15.3-18.0 years]) and 53 control participants (30 female participants [57%] and 23
male participants [43%]; median age, 16.4 years [IQR, 14.8-18.0 years]) completed the PRL task
between January 2014 and March 2020. In total, 27 youths with OCD (18 female patients [67%] and
9 male patients [33%]; median age, 16.1 years [IQR, 15.2-17.2 years]) and 46 control participants (28
female participants [61%] and 18 male participants [39%]; median age, 17.2 years [IQR, 16.3-17.6
years]) completed the WCST between January 2018 and November 2020. For the PRL sample, 30 of
50 patients were receiving selective serotonin reuptake inhibitors (SSRIs) at the time of the study.
Of these patients, 20 received sertraline (mean [SD] dose, 126.25 [54.70] mg), and 10 received
fluoxetine (mean [SD] dose, 35.00 [17.16] mg). For the WCST sample, 11 patients received SSRIs, and
16 patients were unmedicated; 8 patients received sertraline (mean [SD] dose, 118.75 [53.03] mg),
and 3 patients received fluoxetine (mean [SD] dose, 36.67 [15.28] mg).

Standard PRL Results

The patient and control groups were matched for age, IQ, and sex (Table 1). Analyses indicated
significant interactions between group and phase on proportion of correct choices (estimated
coefficient = −0.98; 95% CI, −1.31 to −0.64), proportion of switching in response to spurious (false)
negative feedback (estimated coefficient = 0.93; 95% CI, 0.60-1.26), and proportion of staying in
response to veridical (true) positive feedback (estimated coefficient = −1.74; 95% CI, −2.17 to −1.31)
(Table 2; eFigure 1 in the Supplement). Those results indicated that, during the reversal phase,
compared with controls, patients with OCD made significantly fewer correct responses (mean [SD]
proportion: 0.83 [0.16] for controls vs 0.61 [0.31] for patients), switched more following spurious
(false) negative feedback (mean [SD] proportion: 0.09 [0.16] for controls vs 0.27 [0.34] for patients),
and stayed less following veridical (true) positive feedback (mean [SD] proportion: 0.93 [0.17] for

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controls vs 0.73 [0.34] for patients; 95% CI, −2.17 to −1.31). Significant results persisted when
controlling for covariates (eTable 1 in the Supplement). When stratified by medication, the
unmedicated and medicated groups showed reduced proportion of correct choices (control vs
unmedicated patients: estimated coefficient = 1.35 [95% CI, 0.50-2.2]; control vs medicated:
estimated coefficient = 1.14 [95% CI, 0.39-1.88]; unmedicated vs medicated: estimated
coefficient = −0.21 [95% CI, −1.14 to 0.72]) and proportion of staying in response to veridical (true)
positive feedback (control vs unmedicated patients: estimated coefficient = 2.95 [95% CI,
0.83-5.08]; control vs medicated: estimated coefficient = 2.68 [95% CI, 0.79-4.57]; unmedicated vs
medicated: estimated coefficient = −0.27, [95% CI, −2.48 to 1.93]) compared with the control group
during the reversal phase, but there were no significant differences between the unmedicated and

Table 1. Summary of Demographic and Clinical Measures for the PRL Task, Control vs OCD Groupsa
Abbreviations: BAI, Beck Anxiety Inventory (t-scored);
Mean (SD) value BDI, Beck Depression Inventory (t-scored); CY-BOCS,
Measure Control (n = 53) OCD (n = 50) Mean or median difference (95% CI) P value Child Yale-Brown Obsessive-Compulsive Scale; IQ,
intelligence quotient; NA, not applicable; OCD,
Sex, No. (%)
obsessive-compulsive disorder; OCI, Obsessive-
Girls 30 (56.6) 29 (58.0) Compulsive Inventory; PRL, probabilistic reversal
NA .89
Boys 23 (43.4) 21 (42.0) learning; WASI-II, Weschler Abbreviated Scale of
Intelligence–II.
Age, median (IQR), y 16.4 (14.8-18.0) 16.6 (15.3-18.0) 0.22 (−1.03 to 0.56) .66
a
Mean (SD) values reported for normally distributed
WASI-II (IQ) scoreb,c 109.11 (10.79) 106.57 (12.10) 2.54 (−1.95 to 7.04) .27
data; median (IQR) values, for nonnormally
BDI scorec,d 46.81 (6.43) 59.32 (10.76) −12.51 (−16.01 to −9.00) <.001 distributed data.
c,d
BAI score 48.04 (7.09) 62.82 (11.29) −14.78 (−18.50 to −11.06) <.001 b
Missing data from 1 participant with OCD.
OCI score, 8 (4-14) 27 (18-36) −19.00 (−23.00 to −15.00) <.001 c
Descriptions of clinical questionnaires can be found
median (IQR)c,d
in the eMethods in the Supplement.
CY-BOCS scoreb,c NA 23.47 (5.14) NA NA d
Significant at P < .05.

Table 2. Summary of PRL Measures and Analysis, Control vs OCD Groups

Mean (SD) value

Acquisition Reversal
BH-adjusted
DV and IV Estimated coefficient (95% CI) P value P value Test used Control OCD Control OCD
Proportion of correct choices
Group −0.24 (−0.75 to 0.26) .34 .34
Phase −1.66 (−1.92 to −1.42) <.001 <.001 Binomial mixed
0.96 (0.11) 0.94 (0.10) 0.83 (0.16) 0.61 (0.31)
model
Group × phase −0.98 (−1.31 to −0.64) <.001 <.001
Reaction time, ms
Group 93.52 (−51.72 to 238.77) .21 .27
Phase −60.52 (−118.32 to −2.72) .04 .04 Mixed linear 1035.92 1129.45 975.41 1000.84
model (401.98) (428.97) (355.06) (308.71)
Group × phase −68.09 (−151.05 to 14.87) .11 .11
Proportion of switching in
response to spurious (false)
negative feedback
Group 1.04 (−0.19 to 2.27) .10 .16
Phase 0.50 (0.25 to 0.75) <.001 <.001 Binomial mixed
0.06 (0.14) 0.12 (0.21) 0.09 (0.16) 0.27 (0.34)
model
Group × phase 0.93 (0.60 to 1.26) <.001 <.001
Proportion of staying in response
to veridical (true) positive
feedback
Group −1.05 (−2.20 to 0.09) .72 .16
Phase −0.94 (−1.27 to −0.61) <.001 <.001 Binomial mixed
0.97 (0.10) 0.95 (0.08) 0.93 (0.17) 0.73 (0.34)
model
Group × phase −1.74 (−2.17 to −1.31) <.001 <.001
Proportion of perseverative errors
(only during reversal phase)
Group 0.74 (0.57 to 0.92) .02 .08 Binomial model NA NA 0.11 (0.13) 0.21 (0.27)

Abbreviations: BH, Benjamini-Hochberg correction; OCD, obsessive-compulsive disorder; DV, dependent variable; IV, independent variable; NA, not applicable; p(perseverative
error); PRL, probabilistic reversal learning.

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medicated subgroups. Post hoc group comparisons for proportion of switching in response to
spurious (false) negative feedback were not significant (eTables 2, 3, 4, and 5 and eFigure 2 in the
Supplement).

PRL Modeling
Compared with the control group, patients with OCD displayed increased reward rates (MD, 0.21
[95% HDI, 0.04-0.38]), lower punishment rates (MD, −0.29 [95% HDI, −0.39 to −0.18]), lower
reinforcement sensitivity (MD, −4.91 [95% HDI, −9.38 to −1.12]), and lower stickiness (MD, −0.35
[95% HDI, −0.57 to −0.11]). The unmedicated and medicated subgroups also differed from the
control group on all parameters, showing increased reward rates (unmedicated vs controls: MD, 0.20
[95% HDI, 0.0007-0.39]; medicated vs controls: MD, 0.24 [95% HDI, 0.04-0.41]) but decreased
punishment rates (unmedicated vs controls: MD, −0.32 [95% HDI, −0.44 to −0.18]; medicated vs
controls: MD, −0.28 [95% HDI, −0.39 to −0.16]), reinforcement sensitivity (unmedicated vs controls:
MD, −5.73 [95% HDI, −10.37 to −1.39; medicated vs controls: MD, −4.85 [95% HDI, −9.39 to −0.59]),
and stickiness (unmedicated vs controls: MD, −0.28 [95% HDI, −0.57 to −0.006; medicated vs
controls: MD, −0.40 [95% HDI, −0.65 to −0.12). There were no differences between unmedicated
and medicated patients across these 4 parameters (Figure 2A and B).

Standard WCST Results

Youths in the OCD and control groups were matched for age, IQ, and sex and were equivalent on all
WCST outcome measures when controlling for multiple comparisons (Table 3; eTables 6 and 7 and
eFigure 3 in the Supplement). However, when subdividing the OCD group by medication status,
there was a significant association of group with RT (estimated coefficient = 138.29; 95% CI, 50.40-
226.18) and proportion of unique errors (estimated coefficient = 0.89; 95% CI, 0.29-1.51). Post hoc
comparisons indicated that patients who received medication (mean [SD], 1738.25 [349.23]
milliseconds) displayed significantly slower mean (SD) response times than control participants
(1420.49 [279.71] milliseconds) but not slower than patients who received no medication (1471.42
[212.81] milliseconds) (control vs medicated: MD, −320.26 [95% CI, −547.00 to −88.68]; medicated
vs unmedicated: MD, −269.33 [95% CI, −534 to 0.50]; unmedicated vs control: MD, −50.93 [95%
CI, −249.00 to 147.17]). Moreover, patients who received medication (mean [SD] proportion, 0.008
[0.01]) showed increased unique errors compared with control participants (mean [SD] proportion,
0.001 [0.004]), but there were no significant differences between patients who did and who did
not receive medication (mean [SD] proportion, 0.002 [0.004]), nor between control participants
and patients who received no medication (control vs medicated: MD, −0.007 [95% CI, −3.14 to
−0.36]; medicated vs unmedicated: MD, −0.006 [95% CI, −2.77 to 0.45]; unmedicated vs control:
MD, −0.001 [95% CI, −2.29 to 1.14]). Significant group differences were maintained when controlling
for covariates (eTables 8, 9, 10, and 11 and eFigure 4 in the Supplement).

WCST Modeling
There were no differences between youths in the OCD and control groups on reward rate (MD, 0.005
[95% HDI, −0.04 to 0.05], punishment rate (MD, −0.02 [95% HDI, −0.12 to 0.09], and decision
consistency (MD, −0.15 [95% HDI, −0.51 to 0.22] parameters, or among comparisons of youths in the
unmedicated, medicated, and control groups on these 3 parameters (Figure 2C and D).

Discussion
This is the first study, to our knowledge, to fractionate cognitive processes contributing to behavior
on set-shifting and decision-making paradigms in large samples of youths with OCD. We sought to
understand whether youths 12 to 19 years of age with OCD, similar to adult patients with OCD, show
altered choices when outcomes are either deterministic or probabilistic. On the PRL task, patients
with OCD made significantly more incorrect responses and showed more switching following

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spurious (false) negative feedback and veridical (true) positive feedback in the reversal phase. Our
computational modeling results indicated that, compared with healthy participants, the young
patients with OCD, regardless of medication status, had increased reward rates and choice
exploration (low reinforcement sensitivity) alongside lower punishment rates and stickiness. Youths
with OCD had intact WCST performance and did not differ from control participants on any model
parameters investigated. However, patients who received medication exhibited slower response
times and increased unique errors compared with healthy controls.
The increased exploration displayed by patients with OCD indicates fewer value-driven
decisions (ie, a greater tendency to choose the less optimal stimulus), whereas lower stickiness
signifies increased switching between choices. Recent findings denote choice volatility on
probabilistic reversal tasks to be a key feature of OCD.12,25 The present study contributes to an
emerging literature showing that choice volatility also exists in youths with OCD during probabilistic
tasks. The increased exploration and lower stickiness observed may have resulted from increased
uncertainty regarding choices because patients with OCD commonly report more subjective
uncertainty than healthy people do.26 By contrast, the deterministic feedback on the WCST triggers
less uncertainty. Indeed, increased information-seeking behavior and exploration have been

Figure 2. Computational Modeling Results From the Wisconsin Card Sorting Task (WCST)
and the Probabilistic Reversal Learning (PRL) Task

A PRL model parameters (CTL vs OCD)

Reward rate
Punishment rate
Reinf. sensitivity
Stimulus stickiness

–12 –10 –8 –6 –4 –2 0 2
Mean difference (90% or 95% HDI)
B PRL model parameters (CTL vs UNMED vs MED)
Reward rate: MED vs CTL
Reward rate: UNMED vs CTL
Reward rate: UNMED vs MED
Punishment rate: MED vs CTL
Punishment rate: UNMED vs CTL
Punishment rate: UNMED vs MED
Reinf. sensitivity: MED vs CTL
Reinf. sensitivity: UNMED vs CTL
Reinf. sensitivity: UNMED vs MED
Stimulus stickiness: MED vs CTL
Stimulus stickiness:UNMED vs CTL
Stimulus stickiness: UNMED vs MED

–12 –10 –8 –6 –4 –2 0 2 Error bars in orange indicate credible differences in

C WCST model parameters (CTL vs OCD)
Reward rate
Punishment rate
Decision consistency
–0.6
D WCST model parameters (CTL vs UNMED vs MED)
Reward rate: MED vs UNMED
Reward rate: MED vs CTL
Reward rate: UNMED vs CTL
Punishment rate: MED vs UNMED
Punishment rate: MED vs CTL
Punishment rate: UNMED vs CTL
Decision consistency: MED vs UNMED
Decision consistency: MED vs CTL
Decision consistency: UNMED vs CTL
–1.00 –0.75
Mean difference (90% or 95% HDI) posterior distributions between groups of patients
with obsessive-compulsive disorder (OCD) and control
(CTL) participants (not including 0) within a 95%
highest density interval (HDI). A and B, Results from a
winning computational model for the PRL task. A,
Patients with OCD show increased reward rates but
–0.4 –0.2 0 0.2 0.4 decreased punishment rates, reinforcement (Reinf.)
Mean difference (90% or 95% HDI) sensitivity, and stickiness. B, Patients who were
unmedicated (UNMED) and patients who were
medicated (MED) show increased reward rates but
decreased punishment rates, reinforcement
sensitivity, and stickiness compared with CTL. There
are no noticeable differences in parameter values
between UNMED and MED groups. C and D, Results
from a winning computational model for WCST. C, No
noticeable differences in parameter values between
OCD and CTL groups. D, No noticeable differences in
parameter values between UNMED, MED, and CTL
–0.50 –0.25 0 0.25 0.50 groups. For each parameter, the longer whiskers are
Mean difference (90% or 95% HDI) 90% HDIs, and the shorter whiskers are 95% HDIs.

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 JAMA Network Open | Psychiatry Environmental Uncertainty, Decision-making, and Learning Mechanisms in OCD

detected in adults and children with OCD, particularly on tasks in which uncertainty is enhanced or
when payoffs are probabilistic.17,27-29 Anxiety is commonly evoked by uncertainty,30 and it is
plausible that the stress experienced by patients led to disorganized patterns of responding.
Response volatility may also result from attentional lapses, which may affect learning and is
consistent with research reporting learning impairments in juvenile patients with OCD.16
Elevated reward and reduced punishment rates in our sample of youths with OCD is a novel
finding because prior studies typically report increased sensitivity to negative feedback in adults with
OCD.31-33 By contrast, decreased frontostriatal brain activation following positive and negative
feedback has been detected in children with OCD compared with controls,18 suggesting blunted
feedback processing in young patients. Emerging research reveals that healthy younger people are
significantly more punishment averse than healthy adults.34 In contrast to healthy youths, those with
OCD may not be particularly sensitive to either kind of feedback given that they favor exploratory
over value-driven decision-making. This account is compatible with the clinical presentation of OCD
in which patients’ thoughts and rituals are out of proportion to the information available in the
external environment. A competing explanation is that anxiety experienced by patients enhanced
learning about positive outcomes but decreased avoidance of punishment, a phenomenon
previously shown by inducing stress in healthy people and possibly associated with modulation of
the dopaminergic reward system.35,36
Because youths with OCD in this study did not differ from healthy controls on the proportion of
perseverative errors made on the WCST, we conclude an absence of a cognitive flexibility deficit in
this sample, consistent with previous findings.3 This strengthens the notion that youths with OCD
differ cognitively from adult patients because the latter tend to show deficits on this task.15,37,38
Hence, it is plausible that cognitive flexibility becomes increasingly affected as a function of the
duration of the disorder. There may also be phenotypic differences between child and adult subtypes
of OCD given that cognitive inflexibility is considered a genetic marker for disorder risk.2,39 Future
longitudinal research would be appropriate for probing competing explanations for distinctions
between subtypes.

Table 3. Summary of Clinical, Demographic, and Wisconsin Card Sorting Task Outcome Scores (Control vs OCD)a

Mean (SD)
Mean or median difference
Outcome Control (n = 46) OCD (n = 27) (95% CI) P valueb
Sex, No. (%)
Girls 28 (60.9) 18 (66.7)
NA .62
Boys 18 (39.1) 9 (33.3)
Age, median (IQR), y 17.2 (16.3-17.6) 16.1 (15.2-17.2) 1.09 (−0.08 to 1.42) .07
WASI-II (IQ) scorec 107.61 (11.62) 107.12 (13.02) −0.49 (−5.69 to 6.68) .87
BDI scored 46.46 (5.27) 59.04 (9.55) −12.58 (−16.63 to −8.53) <.001
Abbreviations: BAI, Beck Anxiety Inventory (t-scored);
BAI score, median (IQR)d 46 (44-50) 64 (59-69) −18 (−22 to −14) <.001
d
BDI, Beck Depression Inventory (t-scored); BH,
OCI score, median (IQR) 6.5 (4.0-11.0) 28.0 (23.5-36.5) −21.5 (−26.0 to −18.0) <.001
Benjamini-Hochberg correction; CY-BOCS, Child Yale-
CY-BOCS scorec NA 23.62 (4.84) NA NA Brown Obsessive-Compulsive Scale; IQ, intelligence
No. of sets completed 7.96 (1.48) 7.52 (2.03) −0.44 (−1.26 to 0.38) BH-adjusted quotient; NA, not applicable; OCD, obsessive-
P = .34 (−0.44) compulsive disorder; OCI, Obsessive-Compulsive
Proportion of 0.12 (0.03) 0.13 (0.07) 0.01 (−0.14 to 0.26) BH-adjusted Inventory; WASI-II, Weschler Abbreviated Scale of
perseverative errors P = .54 (0.06)
Intelligence–II.
Proportion of 0.06 (0.04) 0.08 (0.06) 0.02 (−0.07 to 0.66) BH-adjusted
a
nonperseverative errors P = .21 (0.30) Mean (SD) values are reported for normally
Reaction time, ms 1420.49 (279.72) 1580.13 (301.48) 159.64 (20.47 to 298.80) BH-adjusted distributed data; median (IQR) values are reported
P = .09 (159.64) for nonnormally distributed data.
Failure to maintain set 0.94 (1.06) 1.48 (1.50) 0.54 (−0.05 to 1.15) BH-adjusted b
The BH-corrected P values (and estimated regression
P = .17 (0.55)
coefficients) are reported from regression analyses
No. of trials needed to 14.80 (9.58) 18.15 (15.49) 3.35 (−2.50 to 9.19) BH-adjusted
complete first set P = .34 (3.34) of Wisconsin Card Sorting Task outcome measures.
c
Proportion of unique 0.001 (0.005) 0.005 (0.008) 0.004 (0.16 to 2.44) BH-adjusted Missing data from 1 participant with OCD.
errors P = .12 (1.23) d
Significant at P < .05.

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 JAMA Network Open | Psychiatry Environmental Uncertainty, Decision-making, and Learning Mechanisms in OCD

Patients receiving SSRIs in the present study displayed enhanced unique errors and slower
response times. Unique errors are usually made by very young children,40 who have difficulty
attending to and recognizing different task rules. Hence, the patients in our study who received SSRIs
may have attentional and rule-learning impairments, corroborated by previous findings in
adolescents with OCD.16 The slow responding of patients receiving medication is reminiscent of
research identifying slower goal-directed planning and information-seeking in youths with
OCD.17,41-43 Slowness may arise from either meticulousness or intrusive thoughts of patients
with OCD.44
One other study to date, to our knowledge, has reported adverse effects of SSRIs on WCST
performance in pediatric patients with OCD,45 whereas other studies have reported either null or
positive effects of medication.46,47 An explanation for our findings is that the group receiving
medications may have had a more severe form of the disorder that necessitated treatment with
psychotropic medication. Alternatively, cognitive and memory deficits may occur during early stages
of SSRI treatment,48 potentially associated with anxiolytic effects triggered initially by medication
that improve over time.

Limitations
A limitation of the present study is the relatively small sample of youths with OCD completing the
WCST, particularly when grouped by medication status. Although the models fit to data were well
validated for the specific tasks used, we did not consider alternative models, such as
counterfactual,34 bayesian inference,49,50 and drift-diffusion models,51,52 that may offer alternative
insight into underlying behavior.
To rule out the possibility that group differences were associated with non-OCD symptoms, we
excluded patients with comorbid conditions. However, noncomorbid OCD is not wholly
representative of pediatric patients with OCD, who commonly present with at least 1 comorbid
disorder.53 Future research should recruit a naturalistic sample of patients or classify decision-making
based on comorbidity profiles (eg, OCD with anxiety vs OCD with depression). Finally, future work
should administer cognitive tasks using stimuli that provoke OCD symptoms because results from
such tasks may have clearer clinical implications.

Conclusions
The findings of this cross-sectional study suggested that decision-making was altered in youths with
OCD in a task with probabilistic feedback but was relatively unaffected on the WCST, a deterministic
test of flexibility. Our computational modeling findings suggested that environmental uncertainty
promoted altered feedback learning and enchanced choice exploration in youths with OCD, possibly
by triggering doubt or indecisiveness in these young patients. Moreover, choice vacillation has now
been detected in both adults and adolescents with OCD, suggesting that it is a stable feature of the
disorder.

ARTICLE INFORMATION
Accepted for Publication: October 1, 2021.
Published: November 29, 2021. doi:10.1001/jamanetworkopen.2021.36195
Correction: This article was corrected on December 29, 2021, to fix an error in the byline.
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Marzuki AA
et al. JAMA Network Open.
Corresponding Author: Trevor W. Robbins, PhD, Behavioural and Clinical Neuroscience Institute, University of
Cambridge, Downing Street, Downing Site, Cambridge CB2 3EB, United Kingdom (twr2@cam.ac.uk).
Author Affiliations: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United

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 JAMA Network Open | Psychiatry Environmental Uncertainty, Decision-making, and Learning Mechanisms in OCD

Kingdom (Marzuki, Gottwald, Kanen, Kaser, Sahakian, Robbins); Department of Psychology, University of
Cambridge, Cambridge, United Kingdom (Marzuki, Tomić, Kanen, Robbins); International University Malaya–
Wales, Kuala Lumpur, Malaysia (Marzuki); Department of Public Health and Primary Care, School of Clinical
Medicine, University of Cambridge, Cambridge, United Kingdom (Ip); Department of Psychiatry, School of Clinical
Medicine, University of Cambridge, Cambridge, United Kingdom (Gottwald, Sule, Sahakian); Cambridgeshire and
Peterborough NHS Foundation Trust, Cambridge, United Kingdom (Kaser, Conway-Morris).
Author Contributions: Dr Marzuki had full access to all of the data in the study and takes responsibility for the
integrity of the data and the accuracy of the data analysis.
Concept and design: Marzuki, Sule, Conway-Morris, Sahakian, Robbins.
Acquisition, analysis, or interpretation of data: Marzuki, Tomić, Ip, Gottwald, Kanen, Kaser, Conway-
Morris, Robbins.
Drafting of the manuscript: Marzuki, Sahakian, Robbins.
Critical revision of the manuscript for important intellectual content: Tomić, Ip, Gottwald, Kanen, Kaser, Sule,
Conway-Morris, Sahakian, Robbins.
Statistical analysis: Marzuki, Tomić, Kanen.
Obtained funding: Robbins.
Administrative, technical, or material support: Ip, Sule, Conway-Morris, Robbins.
Supervision: Kanen, Kaser, Conway-Morris, Robbins.
Conflict of Interest Disclosures: Dr Gottwald reported receiving personal fees and being currently employed by
PEIX Healthcare Communication outside the submitted work. Dr Kaser reported receiving grants and Clinical
Lectureship support from the National Institute of Health Research during the conduct of the study. Dr Sahakian
reported consulting for Cambridge Cognition and for Greenfield Bioventures outside the submitted work. Dr
Robbins reported receiving personal fees from Cambridge Cognition outside the submitted work. No other
disclosures were reported.
Funding/Support: This research was funded in whole by Wellcome Trust grant 104631/Z/14/Z/ to Dr Robbins.
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and
decision to submit the manuscript for publication.
Additional Information: For the purpose of open access, the author has applied a CC-BY public copyright license
to any Author Accepted Manuscript version arising from this submission.

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 JAMA Network Open | Psychiatry Environmental Uncertainty, Decision-making, and Learning Mechanisms in OCD

SUPPLEMENT.
eMethods. Supplemental Methods
eTable 1. Standard Mixed Regression Results for PRL Covarying for Age, Gender, and IQ
eFigure 1. Group Comparisons (CTL vs OCD) Across All PRL Measures
eTable 2. Summary Statistics for Demographic and Clinical Measures (CTL vs MED- vs MED+)
eTable 3. Summary Statistics for PRL Task Measures (CTL vs MED- vs MED+)
eTable 4. Standard Regression Results for PRL Without Covariates (CTL vs MED- vs MED+)
eTable 5. Standard Regression Results for PRL Covarying for Age, Gender, and IQ (CTL vs MED- vs MED+)
eFigure 2. Group Comparisons (CTL vs MED- vs MED+) Across All PRL Measures
eTable 6. Standard Regression Results for WCST Without Covariates (CTL vs OCD)
eTable 7. Standard Regression Results for WCST Covarying for Age, Gender, and IQ (CTL vs OCD)
eFigure 3. Group Comparisons (CTL vs OCD) Across All WCST Measures
eTable 8. Summary Statistics for Demographic and Clinical Measures (CTL vs MED- vs MED+)
eTable 9. Scores per Outcome Measure per Group (CTL vs MED- vs MED+)
eTable 10. Standard Regression Results for WCST Without Covariates (CTL vs MED- vs MED+)
eTable 11. Standard Regression Results for WCST Covarying for Age, Gender, and IQ (CTL vs MED- vs MED+)
eFigure 4. Group Comparisons (CTL vs MED- vs MED+) per WCST Measure
eTable 12. Model Comparison Using Bridgesampling (PRL)
eTable 13. Model Comparison Using Bridgesampling (WCST)
eTable 14. Parameter Recovery Analysis With Simulated Data Generated by Best-Fit Computational Model (CTL vs
OCD)
eTable 15. Parameter Recovery Analysis With Simulated Data Generated by Best-Fit Computational Model (CTL vs
MED- vs MED+)
eTable 16. Correlations Between Demographic/Clinical Measures and Model Parameters (PRL)—All Subjects
eTable 17. Correlations Between Demographic/Clinical Measures and Model Parameters (PRL)—CTL Only
eTable 18. Correlations Between Demographic/Clinical Measures and Model Parameters (PRL)—OCD Only
eFigure 5. Plots of Correlations Between Demographic/Clinical Measures and Model Parameters (PRL)
eTable 19. Correlations Between Demographic/Clinical Measures and Model Parameters (WCST)—All Subjects
eTable 20. Correlations Between Demographic/Clinical Measures and Model Parameters (WCST)—CTL Only
eTable 21. Correlations Between Demographic/Clinical Measures and Model Parameters (WCST)—OCD Only
eFigure 6. Plots of Correlations Between Demographic/Clinical Measures and Model Parameters (WCST)
eFigure 7. Modelling Results From 20 OCD and 17 CTL
eReferences.

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