Exposure-based Behavioral Therapy Research Articles

Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction.

Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory.

Therapygenetics: 5-HTTLPR genotype predicts the response to exposure therapy for agoraphobia

This study was intended to assess the extent to which the low-expression allele of the serotonin transporter gene promoter predicts better response to exposure-based behavior therapy in patients with panic disorder with agoraphobia (PDA). Ninety-nine patients with PDA underwent a 1-week in vivo exposure-based behavior therapy program and provided saliva samples to extract genomic DNA and classify individuals according to four allelic forms (SA, SG, LA, LG) of the 5-HTT-linked polymorphic region (5-HTTLPR). We determined whether the 5-HTTLPR genotype predicted change in avoidance behavior in PDA following treatment. After controlling for pre-treatment avoidance behavior, the 5-HTTLPR low-expression genotypes showed a more favorable response to exposure therapy two weeks following treatment, compared to the other patients. This study suggests a genetic contribution to treatment outcome following behavior therapy and implicates the serotonergic system in response to exposure-based treatments in PDA.

Trial spacing during extinction: The role of context–us associations.

Studies of extinction in Pavlovian preparations can identify conditions that make extinction more enduring and increase the benefits of exposure-based behavior therapy. One such potential condition is the use of spaced extinction trials. Nevertheless, contradictory results of spacing extinction trials are found in the existing literature. Here we examine the strength of the association between the extinction context and the unconditioned stimulus as a variable that reconciles the seemingly contradictory prior reports. To assess the role of this variable, we evaluated the effects of extinction trial spacing as a function of the associative status of the extinction context in three lick suppression experiments with rats. In Experiment 1, the associative status of the extinction context was manipulated by giving extinction treatment in either the same context as acquisition or a different context. In Experiment 2, the associative status of the extinction context was initially high as a result of the acquisition context being used for extinction and then it was manipulated through postacquisition context exposure. In Experiment 3, extinction was administered in a context different from that of acquisition and the associative status of the extinction context was manipulated by delivering unsignaled footshock (i.e., the unconditioned stimuli) in the extinction context between acquisition and extinction. In all three experiments, consistently less conditioned suppression was observed with spaced extinction trials relative to massed extinction trials when the associative value of the extinction context was relatively low. In contrast, massed extinction trials produced less conditioned suppression when the associative status of the extinction context was high. Thus, stimulus control after extinction is influenced by an interaction between the intertrial interval during extinction and the associative status of the extinction context.

Evaluating treatment efficacy for obsessive-compulsive disorder: Caveat practitioner

There are potent treatments for obsessive-compulsive disorder, but consumers, scientists, and practitioners face challenges in evaluating claims about their efficacy. The present analysis highlights some difficulties with claims about cognitive therapy, exposure-based behavior therapy, pharmacotherapy, the consensus treatment guidelines, and the OCD spectrum hypothesis, which may obscure understanding of treatment efficacy. The goal is to obviate ambiguities that could weaken the conceptual foundations for clinical judgment.

Cognitive behavioral treatment of posttraumatic stress disorder subsequent to a motor vehicle accident: A case example

A high-functioning 27-year-old male with no prior psychiatric history developed posttraumatic stress disorder and marital problems subsequent to a motor vehicle accident. His treatment with exposure-based behavior therapy was augmented by involving his wife in exposure homework assignments. The additional inclusion of marital sessions that focused on increasing intimacy levels appeared to facilitate recovery. Upon completion of treatment, the patient returned to baseline levels of functioning. At 16-week follow-up, the patient remained asymptomatic. Treatment implications for the interconnection between PTSD symptoms and relationship difficulties are discussed.

Efficacy of telephone-administered behavioral therapy for panic disorder with agoraphobia

The purpose of this study was to determine the efficacy of a structured exposure-based behavior therapy program delivered by telephone to agoraphobic individuals who were isolated from specialized treatment centres. Forty-two individuals with a DSM-III-R diagnosis of panic disorder with agoraphobia who were living in rural areas of Ontario were assigned to either an eight-session telephone behavior therapy program or wait-list control condition. There were significant treatment × time interaction effects on several outcome variables. Patients originally in the wait-list group then received the same type of therapy and they also significantly improved. All treatment gains were maintained at three-month and six-month follow-up. Telephone behavior therapy appears to be a cost-effective and efficacious treatment for agoraphobics living in remote regions where specialized anxiety disorder services are not readily available.

Dental fear treatment outcomes for substance use disorder patients.

In order to examine the clinical treatment outcome for dental fears, we compared the records of 18 phobics who had co-morbid substance use disorder (SUD) with those of 27 subjects who were phobic without concomitant SUD. Outcomes were determined by calculation of changes in the Dental Fear Survey (DFS) score. Subjects were classified by the Structured Clinical Interview for DSM-III-R. All subjects received exposure-based behavioral therapy with or without pharmacological adjuncts. All 27 subjects in the non-SUD group and 15 of 18 (83.3%) of subjects in the SUD group improved. Non-SUD subjects improved more than SUD's on the avoidance and specific fear, but not on the physiological upset, dimensions of the DFS.

Clomipramine, flouxetine, and behavior therapy in the treatment of obsessive-compulsive disorder: A meta-analysis

The most common effective treatments for obsessive-compulsive disorder include clomipramine, flouxetine, and exposure-based behavior therapy. A meta-analysis was conducted on the results from 25 appropriate treatment studies (1975–1991). All three treatments were signifantly effective for most of the outcome variables (overall severity, anxiety, depression). Exposure was not significantly effective for reducing depressed mood. More treatment outcome studies are needed before a clearly superio treatment or combination of treatments can be statistically determined.