Enhanced conditioned eyeblink response acquisition and proactive interference in anxiety vulnerable individuals

In classical conditioning, proactive interference may arise from experience with the conditioned stimulus (CS), the unconditional stimulus (US), or both, prior to their paired presentations. Interest in the application of proactive interference has extended to clinical populations as either a risk factor for disorders or as a secondary sign. Although the current literature is dense with comparisons of stimulus pre-exposure effects in animals, such comparisons are lacking in human subjects. As such, interpretation of proactive interference over studies as well as its generalization and utility in clinical research is limited. The present study was designed to assess eyeblink response acquisition after equal numbers of CS, US, and explicitly unpaired CS and US pre-exposures, as well as to evaluate how anxiety vulnerability might modulate proactive interference. In the current study, anxiety vulnerability was assessed using the State/Trait Anxiety Inventories as well as the adult and retrospective measures of behavioral inhibition (AMBI and RMBI, respectively). Participants were exposed to 1 of 4 possible pre-exposure contingencies: 30 CS, 30 US, 30 CS, and 30 US explicitly unpaired pre-exposures, or Context pre-exposure, immediately prior to standard delay training. Robust proactive interference was evident in all pre-exposure groups relative to Context pre-exposure, independent of anxiety classification, with CR acquisition attenuated at similar rates. In addition, trait anxious individuals were found to have enhanced overall acquisition as well as greater proactive interference relative to non-vulnerable individuals. The findings suggest that anxiety vulnerable individuals learn implicit associations faster, an effect which persists after the introduction of new stimulus contingencies. This effect is not due to enhanced sensitivity to the US. Such differences would have implications for the development of anxiety psychopathology within a learning framework

Inhibited Personality Temperaments Translated Through Enhanced Avoidance and Associative Learning Increase Vulnerability for PTSD

Although many individuals who experience a trauma go on to develop post-traumatic stress disorder (PTSD), the rate of PTSD following trauma is only about 15–24%. There must be some pre-existing conditions that impart increased vulnerability to some individuals and not others. Diathesis models of PTSD theorize that pre-existing vulnerabilities interact with traumatic experiences to produce psychopathology. Recent work has indicated that personality factors such as behavioral inhibition (BI), harm avoidance (HA), and distressed (Type D) personality are vulnerability factors for the development of PTSD and anxiety disorders. These personality temperaments produce enhanced acquisition or maintenance of associations, especially avoidance, which is a criterion symptom of PTSD. In this review, we highlight the evidence for a relationship between these personality types and enhanced avoidance and associative learning, which may increase risk for the development of PTSD. First, we provide the evidence confirming a relationship among BI, HA, distressed (Type D) personality, and PTSD. Second, we present recent findings that BI is associated with enhanced avoidance learning in both humans and animal models. Third, we will review evidence that BI is also associated with enhanced eyeblink conditioning in both humans and animal models. Overall, data from both humans and animals suggest that these personality traits promote enhanced avoidance and associative learning, as well as slowing of extinction in some training protocols, which all support the learning diathesis model. These findings of enhanced learning in vulnerable individuals can be used to develop objective behavioral measures to pre-identify individuals who are more at risk for development of PTSD following traumatic events, allowing for early (possibly preventative) intervention, as well as suggesting possible therapies for PTSD targeted on remediating avoidance or associative learning. Future work should explore the neural substrates of enhanced avoidance and associative learning for behaviorally inhibited individuals in both the animal model and human participants

Learning to Obtain Reward, but Not Avoid Punishment, Is Affected by Presence of PTSD Symptoms in Male Veterans: Empirical Data and Computational Model

Post-traumatic stress disorder (PTSD) symptoms include behavioral avoidance which is acquired and tends to increase with time. This avoidance may represent a general learning bias; indeed, individuals with PTSD are often faster than controls on acquiring conditioned responses based on physiologically-aversive feedback. However, it is not clear whether this learning bias extends to cognitive feedback, or to learning from both reward and punishment. Here, male veterans with self-reported current, severe PTSD symptoms (PTSS group) or with few or no PTSD symptoms (control group) completed a probabilistic classification task that included both reward-based and punishment-based trials, where feedback could take the form of reward, punishment, or an ambiguous “no-feedback” outcome that could signal either successful avoidance of punishment or failure to obtain reward. The PTSS group outperformed the control group in total points obtained; the PTSS group specifically performed better than the control group on reward-based trials, with no difference on punishment-based trials. To better understand possible mechanisms underlying observed performance, we used a reinforcement learning model of the task, and applied maximum likelihood estimation techniques to derive estimated parameters describing individual participants’ behavior. Estimations of the reinforcement value of the no-feedback outcome were significantly greater in the control group than the PTSS group, suggesting that the control group was more likely to value this outcome as positively reinforcing (i.e., signaling successful avoidance of punishment). This is consistent with the control group’s generally poorer performance on reward trials, where reward feedback was to be obtained in preference to the no-feedback outcome. Differences in the interpretation of ambiguous feedback may contribute to the facilitated reinforcement learning often observed in PTSD patients, and may in turn provide new insight into how pathological behaviors are acquired and maintained in PTSD

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Enhanced conditioned eyeblink response acquisition and proactive interference in anxiety vulnerable individuals

In classical conditioning, proactive interference may arise from experience with the conditioned stimulus (CS), the unconditional stimulus (US), or both, prior to their paired presentations. Interest in the application of proactive interference has extended to clinical populations as either a risk factor for disorders or as a secondary sign. Although the current literature is dense with comparisons of stimulus pre-exposure effects in animals, such comparisons are lacking in human subjects. As such, interpretation of proactive interference over studies as well as its generalization and utility in clinical research is limited. The present study was designed to assess eyeblink response acquisition after equal numbers of CS, US, and explicitly unpaired CS and US pre-exposures, as well as to evaluate how anxiety vulnerability might modulate proactive interference. In the current study, anxiety vulnerability was assessed using the State/Trait Anxiety Inventories as well as the adult and retrospective measures of behavioural inhibition (AMBI and RMBI, respectively). Participants were exposed to 1 of 4 possible pre-exposure contingencies: 30 CS, 30 US, 30 CS and 30 US explicitly unpaired pre-exposures, or context pre-exposure, immediately prior to standard delay training. Robust proactive interference was evident in all pre-exposure groups relative to context pre-exposure, independent of anxiety classification, with CR acquisition attenuated at similar rates. In addition, trait anxious individuals were found to have enhanced overall acquisition as well as greater proactive interference relative to non-vulnerable individuals. The findings suggest that anxiety vulnerable individuals learn implicit associations faster, an effect which persists after the introduction of new stimulus contingencies. This effect is not due to enhanced sensitivity to the US. Such differences would have implications for the development of anxiety psychopathology within a learning framework

Facilitated acquisition of eyeblink conditioning in those vulnerable to anxiety disorders

Behavioral inhibition (BI) increases vulnerability to develop anxiety disorders and is typified by avoidance and withdrawal from novel objects, people, and situations. The present study considered the relationship between behavioral inhibition and temperamental risk factors, such as trait anxiety and acquisition rate of a classically conditioned eyeblink response. 174 healthy undergraduate students (mean age 20.3 years, 71.8% female) were given the State-Trait Anxiety Inventory and a battery of self-report measures of behavioral inhibition consisting of the Adult and Retrospective Measures of Behavioural Inhibition (AMBI/RMBI) and the Concurrent and Retrospective Self Report of Inhibition (CSRI/RSRI). Participants then underwent standard delay classical eyeblink conditioning consisting of 45 trials with a 500-ms CS overlapping and co-terminating with a 10-ms airpuff US. Individuals with higher scores on the AMBI and Trait Anxiety Inventory, but not the other measures, showed faster acquisition of a conditioned eyeblink response than individuals with lower scores. Results support a relationship between facilitated acquisition of inter-stimulus relationships and risk for anxiety, and suggest that some measures assessing anxiety vulnerability better capture this relationship than others