1. Advance knowledge of the cognitive and neural mechanisms underlying emotional dysregulation in borderline personality disorder. 2. Advance knowledge on the cognitive and neural mechanisms of dialectical behaviour therapy in borderline personality…
ID
Source
Brief title
Condition
- Personality disorders and disturbances in behaviour
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
During the performance of the tasks we will collect behavioural,
psychophysiological (skin conductance and eye tracking) data and functional
imaging data. We also collect measures of treatment success (by means of two
questionnaires: Outcome Questionnaire and borderline personality disorder
severity index).
Secondary outcome
Results will be related not only to measures of severity of BPD, but also to
self report measurements of reward and punishment sensitivity, of trait and
state anger and anxiety, of impulsivity and of delay discounting. All these
measures are thought to have influence either on the instrumental learning
phase, Pavlovian conditioning or the PIT phase.
Background summary
Impulsive and aggressive disorders have a major impact on society as well as on
the individual. For example, borderline personality disorder, associated with
both impulsiveness and aggression, is a devastating psychiatric condition,
affecting 1%-2% of the population. The functional impairment in patients is
severe. This contributes to the high suicide rate of almost 10%[1, 2]. Moreover
these patients constitute a disproportionately large subset of psychiatric in
and outpatient populations, who consume considerably more (mental) healthcare
resources than other psychiatric patients[3].
A cognitive neuropsychiatric approach is paramount for understanding,
developing and optimizing treatments for these complex neuropsychiatric
disorders. In line with recent advances in this area (e.g. [4]), we anticipate
that individual variability in treatment efficacy can be quantified, as well as
predicted by objective indices of cognitive-affective deficits and their neural
mechanisms. Emotion dysregulatioin is thought to be the core psychological
process in borderline personality disorder. From this perspective we developed
an fMRI-suitable Pavlovian-to-instrumental transfer (PIT) task addressing
emotional/affective regulation of goal-directed instrumental behaviour in a
basic neurocognitive manner.
PIT refers to the phenomenon that Pavlovian cues (which predict reward or
punishment) influence instrumental responding. For instance, aversive cues
(which predict punishment) inhibit appetitive instrumental behaviours (such as
approach), while potentiating aversive instrumental behaviours (such as active
withdrawal and passive avoidance). The Pavlovian conditioned stimuli are
interpreted as emotional stimuli, because they influence the assessment of the
value of (other) stimuli; this assessment of positive and negative value is a
key aspect of emotions. This will be the first study in BPD to assess
interactions between experimentally controlled aversive and appetitive
processes and instrumental decision making by making use of a PIT paradigm
before and after treatment.
The PIT paradigm enables us to assess a neurocognitive hypothesis about the
pathophysiology of borderline personality disorder, but also about the
neurocognitive working of dialectical behaviour therapy. It is important to
evaluate this particular treatment strategy, because it is one of the
world-wide most used and successful psychotherapies in the treatment of
borderline personality disorder. Critically, our paradigm targeted at emotion
regulation sorts with this therapy as the normalisation of emotion
dysregulation lies at the heart of this therapy.
Neuroimaging studies on borderline personality disorder indicate a
dysfunctioning fronto-limbic inhibition system. This system consists of among
others ventromedial and orbitofrontal cortex, amygdala and striatum. These
structures along with the nucleus accumbens are also indicated in animal
research as essential for PIT.
Specifically, we hypothesize that borderline personality disorder is
characterized not just by a failure of aversive processing per se, nor by
impaired instrumental decision making per se, but rather by a failure to adjust
instrumental (goal-directed) decision making based on aversive, but not
appetitive Pavlovian cues (i.e. stimuli that predict reward or punishment).
Thus patients with borderline personality disorder are expected to exhibit
exaggerated inhibition of approach and exaggerated promotion of avoidance, only
in the context of aversive Pavlovian cues. We expect this to be accompanied by
differential responses of amygdala and vmPFC/OFC and a compromised
fronto-limbic connectivity. Furthermore we expect that dialectical behavioural
therapy will improve this fronto-limbic connectivity by imposing more frontal
control. In line with thes predictions we will explore if fronto-limbic
dysfunction is prognostic for treatment success.
Study objective
1. Advance knowledge of the cognitive and neural mechanisms underlying
emotional dysregulation in borderline personality disorder.
2. Advance knowledge on the cognitive and neural mechanisms of dialectical
behaviour therapy in borderline personality disorder. This objective is
twofold: (i) exploring the specific neural mechanisms underlying the treatment
success of dialectical behaviour therapy and (ii) discovering individually
tailored prognostic functional neurocognitive markers.
Study design
An explorative observational study (including a non-experimental initiated
treatment intervention) with age, sex and intelligence matched control subjects
will be employed using functional magnetic resonance imaging (fMRI) for neural
measurements. We will use liquid outcomes for reward and punishment. There will
be two fMRI scanning sessions: one before the start of dialectical behaviour
therapy and one afterwards. Both sessions have the same procedure. The main
task enables the assessment of reward and punishment predictive cues on active
approach versus active withdrawal. Skin conductance and pupil dilation
measurements will be obtained to assess autonomic responsiveness to the cues.
Pre- and post-scanning different questionnaires and neuropsychological tests
will be filled out and performed to control, for instance, for attentional
deficits.
Study burden and risks
Participants will get three appointments. During and before the first
appointment participants will receive information and fill out some
questionnaires, they participate in a diagnostic interviews, and a structural
MRI scan will be made. In this session they will also receive training on the
experimental task they will perform during the scan session. During the second
appointment, participants participate in the experimental task during which
functional imaging data will be collected. The third appoint will be the same
as the second appointment but scheduled after dialectical behaviour group
therapy (approximately 9 months) is finished. In these last two sessions
participants will also be asked to fill out questionnaires regarding
psychological dimensions that might well be expected to change during
therapy/over time (9 months). Collection of data will be carried out at the
Donders Centre for Cognitive Neuroimaging. This does not involve any special
risks.
Kapittelweg 29
6525 EN Nijmegen
NL
Kapittelweg 29
6525 EN Nijmegen
NL
Listed location countries
Age
Inclusion criteria
• Age over 18.
• Group 1: Patients meeting the DSM-IV criteria for BPD and who are enrolled in the pretreatment group for dialectical behaviour group therapy at the Psychiatry Dept of the RUNMC.
• Group 2: Controls, matched for age, gender, and intelligence, not meeting DSM-IV criteria for BPD.
Exclusion criteria
Patients:
we do not exclude patient suffering from several *comorbidities*, for instance mood- or eating disorders, because these are more a rule than an exception in BPD . Most important reasons for this are: (i) that the subgroup of patients with BPD formed by excluding the majority of them is not representative for the clinical population; (ii) we are primarily interested in the effectiveness of the therapy over the whole BPD population rather than the efficacy in a certain small subset. Acceptance of this approach in leading literature on BPD can, for example, be seen in the following publication of Silbersweig and colleagues [16]. ;Healthy controls:
Psychiatric:
• Recurrent Major Depressive disorder or Single Major Depressive disorder within five years.
• Other mood- (e.g. bipolar disorder), anxiety- (e.g. social phobic), psychotic- (e.g. delusional disorder, schizophrenia), pervasive devolpmental- (e.g. autistic disorder), attention-deficit- (e.g. ADHD), eating- (e.g. anorexia nervosa) or personality disorders.
• (Current) substance abuse or dependence
• First degree relatives with DSM IV axis I schizophrenia, or schizophreniform disorder or with bipolar depression, ADHD or BPD.
• Mental retardation;Both patients and healthy controls:
General exclusion criteria for fMRI:
unable to give informed consent, metal implants or splinters, surgical clips, prostheses, artificial heart valves, claustrophobia, electronic equipment in body (such as a pacemaker), pregnancy, and epilepsy.;Psychiatric:
• Bipolar disorder, dementia, schizophrenia, delusional disorder, schizophreniform, schizoaffective disorder, shared psychotic disorder, pervasive devolpmental- (e.g. autistic disorder).
• Current substance dependence.
• First degree relatives with DSM IV axis I schizophrenia, or schizophreniform disorder.
• Mental retardation.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL36001.091.11 |