CBT and the Neural Circuits of Anxiety

Anxiety Clinical Trial

Official title:

The Impact of CBT on Shock-Potentiated Neural Circuity

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05549102
• Other study ID #: 121261
• Secondary ID: 255501
• Status: Recruiting
• Start date: February 2, 2020
• Est. completion date: August 1, 2023

Study information

• Verified date: November 2022
• Source: UCLH/UCL Joint Research Office
• Contact: Millie Lowther
• Phone: 02039872331
• Email: millie.lowther[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study will aim to test whether specific neural circuitry changes, proposed on the basis of a neurocognitive model of anxiety, are a mechanism of action for Cognitive Behavioural Therapy (CBT) interventions. This study aims to provide a theoretical model of the neurobiological mechanisms of CBT's therapeutic effect, where there currently is none, and potentially allow for more targeted/specific approaches to anxiety disorders following the identification of key CBT mechanisms. The ultimate aim is to improve the efficacy of CBT, and more generally, psychological interventions for anxiety disorders.

Description:

To test the hypothesis that the neural circuitry of the amygdala and prefrontal cortex will respond to CBT, the impact of a course of CBT on cortical-subcortical circuitry will be tested via a case-control study in individuals entering Improving Access to Psychological Therapies (IAPT) services (IAPT step 3; i.e., full CBT) for anxiety disorders and individuals in waiting lists. This design leverages the naturalistic waiting times in the clinical service and does not interfere with treatment as usual. Measures of brain region-specific connectivity and emotion-related behavioural performance will be assessed through testing sessions at the University College London (UCL) Institute of Cognitive Neuroscience and the Birkbeck-UCL Centre for NeuroImaging (BUCNI), involving computerised cognitive/psychological tasks and functional magnetic resonance imaging (fMRI).

The aims are to:

1. test whether this circuit responds to a course of CBT, by demonstrating disengagement of the circuit following CBT

2. relate this change in circuit function to behaviour through cognitive measures of emotional processing

3. explore the neurobiological features that distinguish patients who respond to CBT and those who do not

4. compare the data from this study to another on-going study assessing the impact of pharmacological interventions for anxiety, allowing for the comparison of neurobiological mechanisms of psychological vs. pharmacological treatments in anxiety.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 174
• Est. completion date: August 1, 2023
• Est. primary completion date: August 1, 2023
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion Criteria:

• Enrolled in IAPT Step 3 (high intensity service)

• Score of or above 8 on the GAD-7 (indicating moderate anxiety on a standard scale of anxiety; Spitzer et al., 2006)

• Willing and able to provide written consent

Exclusion Criteria:

• Score above 22 on the GAD-7

• Past/present psychotic disorder, bipolar disorder/mania or alcohol/substance use disorder (outside a comorbid psychiatric episode)

• History of medical illness that may impair cognitive function (e.g. serious head injury, endocrine disorder)

• Current psychotropic pharmacological intervention (e.g. SSRIs) or use within 3 months

• MRI contraindications such as pacemaker, aneurysm clip, cochlear implant, neurostimulator, IUD, shrapnel, metal fragments in eye, weight of above 250lbs or claustrophobia

• Females who are pregnant, planning pregnancy, or breastfeeding

Related Conditions & MeSH terms

• Anxiety
• Anxiety Depression
• Anxiety Disorder Generalized
• Anxiety Disorder; Mixed With Depression (Mild)
• Anxiety Disorders
• Anxiety Disorders and Symptoms
• Anxiety Generalized
• CBT
• Depression
• Depressive Disorder
• Disease
• Generalised Anxiety Disorder

Intervention

Behavioral:
• Cognitive Behavioural Therapy
In the Cognitive Behavioural Therapy group (N=87), patients will undergo CBT as part of their routine care in Step 3 of the IAPT programme. This will be administered by suitably trained clinicians. The specification of CBT is as recommended by the National Institute for Health and Care Excellence (NICE) guidelines (CG113 - Generalised anxiety disorder and panic disorder in adults: management). In these guidelines, patients are offered on average, 12-15 hourly, weekly sessions of CBT with a trained and competent practitioners. Therapy sessions involve discussions that identify patterns in thinking or behaviours which may be problematic, and therapists and patients work to set goals to reduce these using cognitive techniques. The principle is to teach the patient how to use CBT techniques in their day-to-day life to promote a lasting effect on mental health. We will test patients before (T1) and after (T2) a course of treatment.

Other:
• Waiting List
In the control group (N=87), we will test patients who are currently seeking (but not undergoing) treatment before (T1) and after a wait (T2) of equivalent time (i.e. waiting list controls)

Locations

Country	Name	City	State
United Kingdom	Institute of Cognitive Neuroscience, University College London	London

Sponsors (4)

Lead Sponsor	Collaborator
UCLH/UCL Joint Research Office	Camden and Islington NHS Trust, Central and North West London NHS Foundation Trust, Medical Research Council

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mood diary	A 'mood diary' will be implemented during the intervention phase which will involve daily self-report rating of mood ('happy', 'anxious' and 'sad')	Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Primary	'Aversive amplification circuit' connectivity	The engagement of the neural circuit of the amygdala, cingulate cortex and prefrontal cortex will be measured via an fMRI analysis technique called a psychophysiological interactions (PPI) analysis. PPI analysis concerns behaviour-specific increases in the relationship across regional brain activity - this means that it can allow one to assess whether two regions (a priori selected ROIs) show increased connectivity during a specific context or behaviour, suggesting a behaviour-specific increase in transfer of information. The output of this analysis will take form of a continuous beta weight - an index of connectivity across two brain regions (amygdala and medial prefrontal cortex), which represents the primary outcome of the study.	Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Cognitive task performance: Loss/risk aversion task	Measures how averse participants are to risk and loss in a mock gambling context	Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Cognitive task performance: Go/no-go task	Measures approach/avoidance behaviours under threat of shock or safe conditions	Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Cognitive task performance: Facial emotional processing task	Measures brain responses to positive, negative and neutral emotions	Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Cognitive task performance: Emotional face recognition task	Measures brain responses during two distinct memory processes - the encoding (learning) and retrieval (remembering) of information	Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Cognitive task performance: Visual affective bias task	Measures biases in patients' cognition towards or away from rewarding stimuli	Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Regional activations during neuroimaging task: Facial emotional processing task	Measures brain responses to positive, negative and neutral emotions	Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Regional activations during neuroimaging task: Emotional face recognition task	Measures brain responses during two distinct memory processes - the encoding (learning) and retrieval (remembering) of information	Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Regional activations during neuroimaging task: Visual affective bias task	Measures biases in patients' cognition towards or away from rewarding stimuli	Day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Clinical symptom measure: Generalised Anxiety Disorder Scale (GAD-7)	Measures symptoms of generalised anxiety, scored between 0-21 with higher scores indicating more severe symptoms	Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Clinical symptom measure: State Trait Anxiety Inventory (STAI)	Measures state and trait anxiety symptoms, scored between 20-80 with higher scores indicating more severe symptoms	Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Clinical symptom measures: Patient Health Questionnaire (PHQ-9)	Measures depressive symptoms, scored between 0-27 with higher scores indicating more severe symptoms	Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Clinical symptom measures: Beck's Depression Inventory (BDI)	Measures depressive symptoms, scored between 0-63 with higher scores indicating more severe symptoms	Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Clinical symptom measures: Catastrophizing questionnaire	Measures catastrophising, scored between 24-120 with higher scores indicating more severe symptoms	Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Clinical symptom measures: Daily Stress Inventory (DSI)	Measures frequency and impact of daily stresses. Frequency scored between 0-58 and impact scored between 0-6, with higher scores indicating more severe stress	Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Clinical symptom measures: Behavioural Inhibition/Behavioural Activation Scales (BIS/BAS)	Measures drive, fun-seeking, reward responsiveness and behavioural inhibition. Behavioural inhibition scored between 7-28, drive between 4-16, fun seeking between 4-16, and reward between 5-20, with higher scores indicating higher levels of those behaviours	Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)
Secondary	Clinical symptom measures: Eysenck Impulsiveness Scale	Measures impulsiveness, venturesomeness and empathy. Impulsivity scored between 0-19, venturesomeness between 0-16, empathy between 0-18, with higher scores indicating higher levels of those traits	Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)