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NCT Number: NCT05549102

CBT and the Neural Circuits of Anxiety

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.

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Key information

Conditions

Generalised Anxiety Disorder Anxiety Anxiety Depression Anxiety Disorder Generalized Anxiety Disorder; Mixed With Depression (Mild) Anxiety Disorders Anxiety Disorders and Symptoms Anxiety Generalized CBT Generalized Anxiety Disorder Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Mental Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year–64 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Institute of Cognitive Neuroscience, University College London

London, WC1N 3AZ, United Kingdom

Location status: Recruiting

Location contact

Oliver J Robinson, PhD

CONTACT

[email protected]

020 7679 1150

Oliver J Robinson, PhD

PRINCIPAL_INVESTIGATOR

About this study

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:

  • test whether this circuit responds to a course of CBT, by demonstrating disengagement of the circuit following CBT
  • relate this change in circuit function to behaviour through cognitive measures of emotional processing
  • explore the neurobiological features that distinguish patients who respond to CBT and those who do not
  • 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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Cognitive Behavioural Therapy

Behavioral

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 names: CBT

Waiting List

Other

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)

Primary outcomes

  1. 'Aversive amplification circuit' connectivity

    Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    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.

Secondary outcomes

  1. Cognitive task performance: Loss/risk aversion task

    Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures how averse participants are to risk and loss in a mock gambling context

  2. Cognitive task performance: Go/no-go task

    Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures approach/avoidance behaviours under threat of shock or safe conditions

  3. Cognitive task performance: Facial emotional processing task

    Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures brain responses to positive, negative and neutral emotions

  4. Cognitive task performance: Emotional face recognition task

    Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures brain responses during two distinct memory processes - the encoding (learning) and retrieval (remembering) of information

  5. Cognitive task performance: Visual affective bias task

    Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures biases in patients' cognition towards or away from rewarding stimuli

  6. Regional activations during neuroimaging task: Facial emotional processing task

    Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures brain responses to positive, negative and neutral emotions

  7. Regional activations during neuroimaging task: Emotional face recognition task

    Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures brain responses during two distinct memory processes - the encoding (learning) and retrieval (remembering) of information

  8. Regional activations during neuroimaging task: Visual affective bias task

    Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures biases in patients' cognition towards or away from rewarding stimuli

  9. Clinical symptom measure: Generalised Anxiety Disorder Scale (GAD-7)

    Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures symptoms of generalised anxiety, scored between 0-21 with higher scores indicating more severe symptoms

  10. Clinical symptom measure: State Trait Anxiety Inventory (STAI)

    Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures state and trait anxiety symptoms, scored between 20-80 with higher scores indicating more severe symptoms

  11. Clinical symptom measures: Patient Health Questionnaire (PHQ-9)

    Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures depressive symptoms, scored between 0-27 with higher scores indicating more severe symptoms

  12. Clinical symptom measures: Beck's Depression Inventory (BDI)

    Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures depressive symptoms, scored between 0-63 with higher scores indicating more severe symptoms

  13. Clinical symptom measures: Catastrophizing questionnaire

    Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    Measures catastrophising, scored between 24-120 with higher scores indicating more severe symptoms

  14. Clinical symptom measures: Daily Stress Inventory (DSI)

    Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    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

  15. Clinical symptom measures: Behavioural Inhibition/Behavioural Activation Scales (BIS/BAS)

    Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    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

  16. Clinical symptom measures: Eysenck Impulsiveness Scale

    Time frame: Screening, day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    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

Other outcomes

  1. Mood diary

    Time frame: Day 0, up to 12 weeks (post-CBT or matched time on waiting list)

    A 'mood diary' will be implemented during the intervention phase which will involve daily self-report rating of mood ('happy', 'anxious' and 'sad')

Study contacts

Contact information is provided by the study sponsor or research team.

Emily Lewis

CONTACT

[email protected]

02039872331

Oliver Robinson

CONTACT

[email protected]

02076791150

Sponsors and collaborators

Lead sponsor

UCLH/UCL Joint Research Office

Other

Collaborators

  • Camden and Islington NHS Trust
  • Central and North West London NHS Foundation Trust
  • Medical Research Council

Registry information

Official study title

The Impact of CBT on Shock-Potentiated Neural Circuity

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
Sep 22, 2022
Registry last updated
Jun 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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