Facilitation of Extinction of Conditioned Fear by D-Cycloserine

Abstract— Excessive fear and anxiety are characteristic of disorders such as post-traumatic stress disorder (PTSD) and phobias and are believed to reflect abnormalities in neural systems governing the development and reduction of conditioned fear. Conditioned fear can be suppressed through a process known as extinction, in which repeated exposure to a feared stimulus in the absence of an aversive event leads to a gradual reduction in the fear response to that stimulus. Like conditioned fear learning, extinction is dependent on a particular protein (the N-methyl-D-aspartate or NMDA receptor) in a part of the brain called the amygdala. Blockade of this receptor blocks extinction and improving the activity of this receptor with a drug called D-cycloserine speeds up extinction in rats. Because exposure-based psychotherapy for fear disorders in humans resembles extinction in several respects, we investigated whether D-cycloserine might facilitate the loss of fear in human patients. Consistent with findings from the animal laboratory, patients receiving D-cycloserine benefited more from exposure-based psychotherapy than did placebo-treated controls. Although very preliminary, these data provide initial support for the use of cognitive enhancers in psychotherapy and demonstrate that preclinical studies in rodents can have direct benefits to humans.     

Factors predictive of a fetal alcohol spectrum disorder diagnosis: Parent and teacher ratings

Diagnostic assessment in Fetal Alcohol Spectrum Disorder (FASD) is informed by multidisciplinary assessment incorporating objective (i.e., test measures) and subjective means, such as parent and teacher behavior ratings. The purpose of this study was to extend our previous neuropsychological test findings by identifying parent and teacher ratings of academic achievement, attention, executive functioning, and adaptive functioning as predictors of an FASD diagnosis. The charts of 315 children and adolescents with prenatal alcohol exposure (PAE) who underwent assessment for FASD were retrospectively reviewed. Direct logistic regressions analyzed the contribution of different ratings on the likelihood of an FASD diagnosis. The results suggest that a number of rating measures do contribute toward accurately differentiating those with FASD from within a PAE population, including teacher ratings of learning problems, inattention, and adaptive skills. The classification accuracy for each regression was clinically significant (59.1–70.8%). Children with worse ratings on these variables are approximately 1.5 to 2 times more likely to receive an FASD diagnosis. Only teacher ratings (not parent) significantly contributed to whether a diagnosis was made, suggesting that teacher observational rating scales are a critical component of an FASD assessment. Together with our previous research examining neuropsychological evaluation and FASD diagnostic assessment, this study helps to further guide decisions to streamline care in multidisciplinary assessment and intervention planning.     

Affect Labeling to Facilitate Inhibitory Learning: Clinical Considerations

Exposure-based treatments known to be effective for a wide range of psychopathology are thought to work via inhibitory learning, where new learning acquired during exposure exercises inhibits previously learned fear and avoidance responses. One way in which this inhibitory learning may be enhanced is through affect labeling, during which clients verbalize their internal emotional experiences. Theoretically, affect labeling may be a subtle, implicit form of emotion regulation and may facilitate more explicit forms of extinction learning. Experimental research suggests that affect labeling may lead to attenuated fear responses to emotionally evocative stimuli in healthy samples and may be a helpful strategy in reducing physiological arousal experienced during exposure tasks, particularly for clients with inhibitory deficits. Research with clinical samples is limited and mixed, at best. Case examples illustrate how affective labeling may help get a client “unstuck” from unproductive processing loops, can contribute to shifts in perspective and meaning making, and may modulate distress and promote distress tolerance. We argue that routine use of affect labeling in clinical care is premature. When used, it should be employed strategically within a broader case conceptualization and may be of a limited benefit beyond what is already employed in quality exposure therapy.     

Hope for the Worst: Occasional Reinforced Extinction and Expectancy Violation in the Treatment of OCD

An inhibitory learning conceptualization of treatment mechanisms in exposure-based therapy appears to better account for durability of symptom reduction and index overall learning. Presented here is an overview of two core elements of inhibitory learning, expectancy violation and occasional reinforced extinction, as they are thought to function in exposure and response prevention (ERP) for OCD. The overview is then followed by case examples illustrating these processes at work in a naturalistic clinical setting. Implications for treatment are broadly discussed.     

Treating obsessive compulsive behavior and enhancing peer engagement in a preschooler with intellectual disability

Intellectual disability (ID) is a neurodevelopmental disorder characterized by impairments in cognitive and adaptive functioning in social, practical, or conceptual domains. Individuals with ID present with higher‐order repetitive behaviors such as a need for sameness, ritualistic, and compulsive behaviors. Often referred to as obsessive compulsive behaviors (OCBs), these behaviors increase in prevalence between 2 and 5 years of age. The present study evaluated an exposure‐based behavioral intervention for decreasing OCBs and concomitantly increasing play skills in a 4‐year‐old boy with mild ID in an inclusive preschool setting. Using a multiple baseline across behaviors design, the intervention was associated with a decrease in target behaviors and an increase in the duration of peer social engagement, with results maintained at 3‐week follow‐up. The intervention consisted of exposure and response prevention with function‐based components. Procedures including prompting and reinforcement were generalized to parent and teacher mediators. This study provides preliminary support for the use of an exposure‐based behavioral intervention to treat OCBs in children of preschool age with ID.     

Effects of decreasing intersession interval duration on graduated exposure treatment during simulated routine dental care

Reports suggest that individuals with developmental disabilities often engage in behavior during dental visits that precludes regular dental care. Graduated exposure therapies are an effective treatment for avoidant behavior in people with developmental delays, and some studies show that the duration of the intersession interval (ISI) can impact the effectiveness of graduated exposure treatments for typically developing individuals. The current study examined the effects of decreasing ISI on outcomes of a graduated exposure treatment during simulated routine dental care for 3 individuals diagnosed with autism. Treatment consisted of graduated exposure and extinction for disruptive behavior. Initially, sessions were conducted once per week. In subsequent conditions, treatment sessions were conducted 3‐5 times per week. A nonconcurrent multiple baseline across subjects design was used to demonstrate experimental control. Results suggest that decreasing ISI durations can produce improved treatment outcomes.     

Trace administration of vitamin E can retrieve and prevent UV-irradiation- and metal exposure-induced memory deficits in nematode Caenorhabditis elegans

Vitamin E (α-tocopherol), a lipid-soluble anti-oxidant, prevents the uncontrolled propagation of lipid peroxidation by free radicals. Nevertheless, there is weak or no evidence of a protective effect of previous vitamin E intake on cognitive function in humans. In the present study, we explored the thermosensation model to investigate the possible effects of vitamin E administration on memory behaviors in Caenorhabditis elegans. Administration of 100 and 200 μg/mL of vitamin E had no significant effects on the memory for different time intervals, whereas relatively high concentration (400 μg/mL) of vitamin E exposure shortened the extinction period of the association paradigm (food at 20 °C). Following the UV-irradiation, post-treatment with 200 μg/mL of vitamin E not only retrieved the UV-irradiation-induced memory deficits, but also enhanced the memory functions in UV-irradiating animals. Post-treatment with trace vitamin E could also ameliorate the memory deficits in metal (Al or Pb) exposed worms. In addition, pre-treatment with 200 μg/mL of vitamin E could effectively prevent the occurrence of memory deficits induced by metal exposure and UV-irradiation. Therefore, the close association may exist between trace dietary vitamin E intake and memory behaviors, and a specific response mechanism may be activated after the administration of vitamin E in stress-exposed animals. Moreover, treatment with 200 μg/mL of vitamin E could restore the memory deficits formed in the ncs-1 mutant worms, suggesting that exogenous treatment with trace vitamin E can largely mimic the function of NCS-1 in regulating the memory for thermosensation.     

Information integration in multiple cue judgment: a division of labor hypothesis

There is considerable evidence that judgment is constrained to additive integration of information. The authors propose an explanation of why serial and additive cognitive integration can produce accurate multiple cue judgment both in additive and non-additive environments in terms of an adaptive division of labor between multiple representations. It is hypothesized that, whereas the additive, independent linear effect of each cue can be explicitly abstracted and integrated by a serial, additive judgment process, a variety of sophisticated task properties, like non-additive cue combination, non-linear relations, and inter-cue correlation, are carried implicitly by exemplar memory. Three experiments investigating the effect of additive versus non-additive cue combination verify the predicted shift in cognitive representations as a function of the underlying combination rule.     

Subliminal exposure to faces and racial attitudes: Exposure to Whites makes Whites like Blacks less

Despite recent social and political advances, most interracial contact is still superficial in nature, and White individuals interact mainly with other Whites. Based on recent mere exposure research, we propose that repeated exposure to Whites may actually increase prejudice. In a series of experiments, White participants were subliminally exposed to White faces or nothing (control) and then completed various explicit and implicit measures of racial attitudes. Exposure to White faces consistently led to more prejudice by making attitudes toward Blacks more negative, rather than by making attitudes toward Whites more positive. A final experiment demonstrated that the pattern of increased prejudice following exposure to Whites was moderated by the strength of participants’ attitudes toward Whites. Only when White attitudes were strong did Black attitudes became more negative after exposure to White faces.