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25th European Congress of Psychiatry / European Psychiatry 41S (2017) S8–S52


The impact of the change trial on

physical health in people with


M. Nordentoft

1 ,

, H. Speyer


, H.C.B. Norgaard


, M. Birk



O. Mors



Hellerup, Denmark


Mental Health Center Copenhagen, Research Department, Hellerup,



Aarhus University Hospital, Research Department P, Aarhus,


Corresponding author.

Life expectancy in patients with schizophrenia is reduced by 20

years for men and 15 years for women compared to the general

population. About 60% of the excess mortality is due to physical

illnesses, with cardiovascular disease being dominant. The aim of

this trial was to improve the cardiovascular risk profile.


The CHANGE trial was an investigator-initiated, ran-

domised, parallel-group, superiority, multi-centre trial with

blinded outcome assessment. Patients diagnosed with schizophre-

nia spectrum disorders and increased waist circumference

according (>88 cm for women, >102 cm for men), were recruited

and centrally randomised 1:1:1 to 12-months of lifestyle coach-

ing plus care coordination versus care coordination alone versus

treatment as usual. The primary outcome was 10-year risk of car-

diovascular disease assessed post-treatment and standardised to

age 60, secondary outcomes included cardiorespiratory fitness and

physical activity. NCT01585493.


A total of 428 participants were randomly assigned to

the CHANGE intervention (


= 138); care coordination (


= 142); or

treatment as usual (


= 148). At 12 months, the mean 10 years risk

of cardiovascular disease was 8.4% (SD 6.7) in the CHANGE group,

8.5% (SD 7.5) in the care coordination group and 8.0% (SD 6.5) in

the treatment as usual group (


= 0.41). We found no interven-

tion effects for any secondary or explorative outcomes, including

weight, cardiorespiratory fitness, physical activity, diet or smoking.


The CHANGE trial did not support individual

lifestyle coaching or care coordination as superior compared with

treatment as usual in reducing the cardiovascular risk in patients

with schizophrenia and increased waist circumference.

Disclosure of interest

The authors have not supplied their decla-

ration of competing interest.

Symposium: From prediction errors to disorders

of compulsivity: A computational framework


Elucidating the neural circuitry

underlying individual differences in

response to reward-associated cues

S. Flagel


Stimuli in the environment that have been associated with reward

can gain control over behavior and, in some cases, lead to mal-

adaptive behavior. Reward cues acquire inordinate control when

they are attributed with incentive salience or transformed into

“motivational magnets” (i.e. incentive stimuli). Individuals vary

considerably in the extent to which they attribute incentive moti-

vational value to reward cues, and we can capture this individual

variation using an animal model. When rats are exposed to a

Pavlovian conditioning paradigm, in which the presentation of a

lever-cue is immediately followed by the delivery of a food reward,

some rats preferentially approach the lever (sign-trackers, STs)

while others approach the food cup (goal-trackers, GTs). Impor-

tantly, while the lever is a predictor for both STs and GTs, only for

STs does it become an incentive stimulus. Thus, this model allows

us to parse the neurobiological mechanisms underlying predictive

vs. incentive learning processes. Using this model, we have demon-

strated that dopamine is critical for incentive, but not predictive,

learning and that the cortico-thalamic-striatal “motive circuit” is

engaged only by incentive stimuli. In addition, we have identified

the paraventricular nucleus of the thalamus (PVT) as a central node

that differentially regulates sign- and goal-tracking behaviors. We

have begun to utilize a chemogenetic approach (i.e. DREADDs) in

combination with in vivo microdialysis to further elucidate the

neural circuitry underlying individual variation in cue-motivated

behaviors. Findings suggesting that STs rely primarily on subcor-

tical mechanisms, whereas GTs utilize more “top-down” cortical

processes will be presented and discussed.

Disclosure of interest

The author has not supplied his declaration

of competing interest.


A reinforcement-learning account of

Tourette syndrome

T. Maia

Faculdade de Medicina-Universidade de Lisboa, Instituto de Medicina

Molecular, Lisbon, Portugal


Tourette syndrome (TS) has long been thought to

involve dopaminergic disturbances, given the effectiveness of

antipsychotics in diminishing tics. Molecular-imaging studies have,

by and large, confirmed that there are specific alterations in the

dopaminergic system in TS. In parallel, multiple lines of evidence

have implicated the motor cortico-basal ganglia-thalamo-cortical

(CBGTC) loop in TS. Finally, several studies demonstrate that

patients with TS exhibit exaggerated habit learning. This talk will

present a computational theory of TS that ties together these mul-

tiple findings.


The computational theory builds on computational

reinforcement-learning models, and more specifically on a recent

model of the role of the direct and indirect basal-ganglia pathways

in learning from positive and negative outcomes, respectively.


A model defined by a small set of equations that charac-

terize the role of dopamine in modulating learning and excitability

in the direct and indirect pathways explains, in an integrated way:

(1) the role of dopamine in the development of tics; (2) the relation

between dopaminergic disturbances, involvement of the motor

CBGTC loop, and excessive habit learning in TS; (3) the mecha-

nismof action of antipsychotics in TS; and (4) the psychological and

neural mechanisms of action of habit-reversal training, the main

behavioral therapy for TS.


A simple computational model,


grounded on computational theory and basic-science findings

concerning dopamine and the basal ganglia, provides an inte-

grated, rigorous mathematical explanation for a broad range of

empirical findings in TS.

Disclosure of interest

The author has not supplied his declaration

of competing interest.