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Early effects of exposure-based cognitive behaviour therapy on the neural correlates of anxiety.

ABSTRACT: Exposure-based cognitive-behaviour therapy (CBT) for anxiety disorders is an effective intervention, but the brain mechanisms driving recovery are largely unknown. In this experimental medicine study, we investigated to what degree CBT affects neural markers of anxiety at an early stage of treatment, to identify dynamic mechanistic changes which might be crucial in the process of recovery as opposed to those seen following full treatment completion. In a randomised controlled trial, unmedicated patients with panic disorder either received four weekly sessions of exposure-based CBT (N?=?14) or were allocated to a waiting group (N?=?14). Symptom severity was measured before and after the intervention. During functional magnetic resonance imaging (fMRI), patients performed an emotion regulation task, either viewing negative images naturally, or intentionally down-regulating negative affect using previously taught strategies. Four-session CBT led to marked reductions in symptoms and 71% of patients reached recovery status (versus 7% in the control group). This intervention normalised brain hyperactivation previously seen in panic disorder, particularly in areas linked to threat monitoring, fear memory, and maladaptive emotion regulation, such as amygdala, dorsomedial and dorsolateral prefrontal cortex, and temporal gyrus. Our findings suggest that optimal treatment doses for panic disorder might be much lower than previously thought. Furthermore, this is the first study to show that neural markers of anxiety change very early during CBT, highlighting potential neural mechanisms that might drive clinical recovery. Such knowledge is important for the development of more compact combination treatments targeting these mechanisms more effectively. (Neural Effects of Cognitive-behaviour Therapy in Panic Disorder; clinicaltrials.gov; NCT03251235).

SUBMITTER: Reinecke A

PROVIDER: S-EPMC6195621 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Early effects of exposure-based cognitive behaviour therapy on the neural correlates of anxiety.

Reinecke Andrea A Thilo Kai V KV Croft Alison A Harmer Catherine J CJ

Translational psychiatry 20181019 1

Exposure-based cognitive-behaviour therapy (CBT) for anxiety disorders is an effective intervention, but the brain mechanisms driving recovery are largely unknown. In this experimental medicine study, we investigated to what degree CBT affects neural markers of anxiety at an early stage of treatment, to identify dynamic mechanistic changes which might be crucial in the process of recovery as opposed to those seen following full treatment completion. In a randomised controlled trial, unmedicated ...[more]

PMID: 30341276

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Project description:ObjectivesInternet-delivered exposure-based cognitive behaviour therapy (ICBT) has been shown to be effective in the treatment of severe health anxiety. The health economic effects of the treatment have, however, been insufficiently studied and no prior study has investigated the effect of ICBT compared with an active psychological treatment. The aim of the present study was to investigate the cost effectiveness of ICBT compared with internet-delivered behavioural stress management (IBSM) for adults with severe health anxiety defined as Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) hypochondriasis. ICBT was hypothesised to be the more cost-effective treatment.SettingThis was a cost-effectiveness study within the context of a randomised controlled trial conducted in a primary care/university setting. Participants from all of Sweden could apply to participate.ParticipantsSelf-referred adults (N=158) with a principal diagnosis of DSM-IV hypochondriasis, of whom 151 (96%) provided baseline and post-treatment data.InterventionsICBT or IBSM for 12 weeks.Primary and secondary measuresThe primary outcome was the Health Anxiety Inventory. The secondary outcome was the EQ-5D. Other secondary measures were used in the main outcome study but were not relevant for the present health economic analysis.ResultsBoth treatments led to significant reductions in gross total costs, costs of healthcare visits, direct non-medical costs and costs of domestic work cutback (p=0.000-0.035). The incremental cost-effectiveness ratio (ICER) indicated that the cost of one additional case of clinically significant improvement in ICBT compared with IBSM was $2214. The cost-utility ICER, that is, the cost of one additional quality-adjusted life year, was estimated to be $10,000.ConclusionsICBT is a cost-effective treatment compared with IBSM and treatment costs are offset by societal net cost reductions in a short time. A cost-benefit analysis speaks for ICBT to play an important role in increasing access to effective treatment for severe health anxiety.Trial registration numberNCT01673035; Results.

Project description:Pathological fear and anxiety are highly debilitating and, despite considerable advances in psychotherapy and pharmacotherapy they remain insufficiently treated in many patients with PTSD, phobias, panic and other anxiety disorders. Increasing preclinical and clinical evidence indicates that pharmacological treatments including cognitive enhancers, when given as adjuncts to psychotherapeutic approaches [cognitive behavioral therapy including extinction-based exposure therapy] enhance treatment efficacy, while using anxiolytics such as benzodiazepines as adjuncts can undermine long-term treatment success. The purpose of this review is to outline the literature showing how pharmacological interventions targeting neurotransmitter systems including serotonin, dopamine, noradrenaline, histamine, glutamate, GABA, cannabinoids, neuropeptides (oxytocin, neuropeptides Y and S, opioids) and other targets (neurotrophins BDNF and FGF2, glucocorticoids, L-type-calcium channels, epigenetic modifications) as well as their downstream signaling pathways, can augment fear extinction and strengthen extinction memory persistently in preclinical models. Particularly promising approaches are discussed in regard to their effects on specific aspects of fear extinction namely, acquisition, consolidation and retrieval, including long-term protection from return of fear (relapse) phenomena like spontaneous recovery, reinstatement and renewal of fear. We also highlight the promising translational value of the preclinial research and the clinical potential of targeting certain neurochemical systems with, for example d-cycloserine, yohimbine, cortisol, and L-DOPA. The current body of research reveals important new insights into the neurobiology and neurochemistry of fear extinction and holds significant promise for pharmacologically-augmented psychotherapy as an improved approach to treat trauma and anxiety-related disorders in a more efficient and persistent way promoting enhanced symptom remission and recovery.

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Early effects of exposure-based cognitive behaviour therapy on the neural correlates of anxiety.

Publications

Early effects of exposure-based cognitive behaviour therapy on the neural correlates of anxiety.

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