Erin B. Tone

FKBP5 and Attention Bias for Threat: Associations With Hippocampal Function and Shape

IMPORTANCE The FKBP5 gene product regulates glucocorticoid receptor (GR) sensitivity and hypothalamic-pituitary-adrenal axis functioning and has been associated with many stress-related psychiatric disorders. The study of intermediate phenotypes, such as emotion-processing biases and their neural substrates, provides a way to clarify the mechanisms by which FKBP5 dysregulation mediates risk for psychiatric disorders. OBJECTIVE To examine whether allelic variations for a putatively functional single-nucleotide polymorphism associated with FKBP5 gene regulation (rs1360780) would relate differentially to attention bias for threat. this was measured through behavioral response on a dot probe task and hippocampal activation during task performance. Morphologic substrates of differential hippocampal response were also measured. DESIGN Cross-sectional study conducted from 2010 to 2012 examining associations between genotype, behavioral response, and neural response (using functional magnetic resonance imaging [fMRI]) on the dot probe; voxel-based morphometry and global and local shape analyses were used to measure structural differences in hippocampi between genotype groups. SETTING Participants were recruited from primary care clinics of a publicly funded hospital in Atlanta, Georgia. PARTICIPANTS An African American cohort of adults (N = 103) was separated into 2 groups by genotype: one genotype group included carriers of the rs1360780 T allele, which has been associated with increased risk for posttraumatic stress disorder and affective disorders; the other group did not carry this allele. Behavioral data included both sexes (N = 103); the MRI cohort (n = 36) included only women. MAIN OUTCOME MEASURES Behavioral and fMRI (blood oxygen level-dependent) response, voxel-based morphometry, and shape analyses. RESULTS Carriers of the rs1360780 T allele showed an attention bias toward threat compared with individuals without this allele (F1,90 = 5.19, P = .02). Carriers of this allele demonstrated corresponding increases in hippocampal activation and differences in morphology; global and local shape analyses revealed alterations in hippocampal shape for TT/TC compared with CC genotype groups. CONCLUSION Genetic variants of FKBP5 may be associated with risk for stress-related psychiatric disorders via differential effects on hippocampal structure and function, resulting in altered attention response to perceived threat.

Neural Correlates of Attention Bias to Threat in Post-traumatic Stress Disorder

Attentional biases have been proposed to contribute to symptom maintenance in posttraumatic stress disorder (PTSD), although the neural correlates of these processes have not been well defined; this was the goal of the present study. We administered an attention bias task, the dot probe, to a sample of 37 (19 control, 18 PTSD+) traumatized African-American adults during fMRI. Compared to controls, PTSD+ participants demonstrated increased activation in the dorsolateral prefrontal cortex (dlPFC) in response to threat cue trials. In addition, attentional avoidance of threat corresponded with increased ventrolateral prefrontal cortex (vlPFC) and dorsal anterior cingulate cortex (dACC) activation in the PTSD group, a pattern that was not observed in controls. These data provide evidence to suggest that relative increases in dlPFC, dACC and vlPFC activation represent neural markers of attentional bias for threat in individuals with PTSD, reflecting selective disruptions in attentional control and emotion processing networks in this disorder.

Does engagement with exposure yield better outcomes? Components of presence as a predictor of treatment response for virtual reality exposure therapy for social phobia

Virtual reality exposure (VRE) has been shown to be effective for treating a variety of anxiety disorders, including social phobia. Presence, or the level of connection an individual feels with the virtual environment, is widely discussed as a critical construct both for the experience of anxiety within a virtual environment and for a successful response to VRE. Two published studies show that whereas generalized presence relates to fear ratings during VRE, it does not relate to treatment response. However, presence has been conceptualized as multidimensional, with three primary factors (spatial presence, involvement, and realness). These factors can be linked to other research on the facilitation of fear during exposure, inhibitors of treatment response (e.g., distraction), and more recent theoretical discussions of the mechanisms of exposure therapy, such as Boutons description of expectancy violation. As such, one or more of these components of presence may be more strongly associated with the experience of fear during VRE and treatment response than the overarching construct. The current study (N=41) evaluated relations between three theorized components of presence, fear ratings during VRE, and treatment response for VRE for social phobia. Results suggest that total presence and realness subscale scores were related to in-session peak fear ratings. However, only scores on the involvement subscale significantly predicted treatment response. Implications of these findings are discussed.

Vigilant and avoidant attention biases as predictors of response to cognitive behavioral therapy for social phobia.

Background: Attention bias for socially threatening information, an empirically supported phenomenon, figures prominently in models of social phobia. However, all published studies examining this topic to date have relied on group means to describe attention bias patterns; research has yet to examine potential subgroups of attention bias among individuals with social phobia (e.g., vigilant or avoidant). Furthermore, almost no research has examined how attention biases in either direction may predict change in symptoms as a result of treatment. Methods: This study (N = 24) compared responses to cognitive behavioral therapy (CBT) for social phobia between individuals with avoidant and vigilant biases for threatening faces at pretreatment. Results: Participants with avoidant biases reported significantly and clinically higher symptom levels at posttreatment than did those with vigilant biases. Conclusions: These findings suggest that an avoidant attention bias may be associated with reduced response to CBT for social phobia. Depression and Anxiety, 2011.

Neural Responses to Peer Rejection in Anxious Adolescents: Contributions from the Amygdala- Hippocampal Complex

Peer rejection powerfully predicts adolescent anxiety. While cognitive differences influence anxious responses to social feedback, little is known about neural contributions. Twelve anxious and twelve age-, gender- and IQ-matched, psychiatrically healthy adolescents received “not interested” and “interested” feedback from unknown peers during a chat room task administered in a neuroimaging scanner. No group differences emerged in subjective ratings to peer feedback, but all participants reported more negative emotion at being rejected (than accepted) by peers to whom they had assigned high-desirability ratings. Further highlighting the salience of such feedback, all adolescents, independently of anxiety levels, manifested elevated responses in the amygdala-hippocampal complex bilaterally, during the anticipation of feedback. However, anxious adolescents differed from healthy adolescents in their patterns of persistent amygdala-hippocampal activation following rejection. These data carry interesting implications for using neuroimaging data to inform psychotherapeutic approaches to social anxiety.

Associations among perceptual anomalies, social anxiety, and paranoia in a college student sample

Recent evidence suggests that normal-range paranoid ideation may be particularly likely to develop in individuals disposed to both social anxiety and perceptual anomalies. This study was designed to test the hypothesis that among college students in an unselected sample, social anxiety and experience of perceptual anomalies would not only each independently predict the experience of self-reported paranoid ideation, but would also interact to predict paranoid patterns of thought. A diverse sample of 644 students completed a large battery of self-report measures, as well as the five-factor Paranoia/Suspiciousness Questionnaire (PSQ). We conducted hierarchical multiple regression analyses predicting scores on each PSQ factor from responses on measures of social anxiety, perceptual aberration, and the interaction between the two constructs. Current general negative affect was covaried in all analyses. We found that both social anxiety and perceptual aberrations, along with negative affect, predicted multiple dimensions of paranoia as measured by the PSQ; the two constructs did not, however, interact significantly to predict any dimensions. Our findings suggest that perceptual aberration and anxiety may contribute to normal-range paranoid ideation in an additive rather than an interactive manner.

The structure of schizotypal personality traits: a cross-national study

BACKGROUND Schizotypal traits are considered a phenotypic-indicator of schizotypy, a latent personality organization reflecting a putative liability for psychosis. To date, no previous study has examined the comparability of factorial structures across samples originating from different countries and cultures. The main goal was to evaluate the factorial structure and reliability of the Schizotypal Personality Questionnaire (SPQ) scores by amalgamating data from studies conducted in 12 countries and across 21 sites. METHOD The overall sample consisted of 27 001 participants (37.5% males, n = 4251 drawn from the general population). The mean age was 22.12 years (s.d. = 6.28, range 16-55 years). The SPQ was used. Confirmatory factor analysis (CFA) and Multilevel CFA (ML-CFA) were used to evaluate the factor structure underlying the SPQ scores. RESULTS At the SPQ item level, the nine factor and second-order factor models showed adequate goodness-of-fit. At the SPQ subscale level, three- and four-factor models displayed better goodness-of-fit indices than other CFA models. ML-CFA showed that the intraclass correlation coefficients values were lower than 0.106. The three-factor model showed adequate goodness of fit indices in multilevel analysis. The ordinal α coefficients were high, ranging from 0.73 to 0.94 across individual samples, and from 0.84 to 0.91 for the combined sample. CONCLUSIONS The results are consistent with the conceptual notion that schizotypal personality is a multifaceted construct and support the validity and utility of SPQ in cross-cultural research. We discuss theoretical and clinical implications of our results for diagnostic systems, psychosis models and cross-national mental health strategies.

A pilot study of attention bias subtypes: examining their relation to cognitive bias and their change following cognitive behavioral therapy.

OBJECTIVE The present investigation examined (a) whether a clinical sample of individuals with social anxiety disorder (SAD) comprises two distinct groups based on attention bias for social threat (vigilant, avoidant), (b) the relation between attention bias and cognitive bias, specifically estimates of the probability that negative social events will occur (probability bias), and (c) specific changes in attention bias following cognitive behavioral therapy for social anxiety. METHOD Participants were 24 individuals (nfemale = 7, nmale = 17; mage = 41) who met diagnostic criteria for SAD and sought treatment for fear of public speaking. Hypotheses were tested using t tests, linear regression analyses, and a mixed design analysis of variance. RESULTS Results yielded evidence of 2 pretreatment groups (vigilant and avoidant). There was a significant positive correlation between vigilance for (but not avoidance of) threat and probability bias (R = .561, p < .05). After 8 weeks of treatment, the direction of change in attention bias differed between groups, such that the vigilant group became less vigilant and the avoidant group became less avoidant, with the avoidant group showing a significant change in attention bias from pretreatment to posttreatment. CONCLUSIONS These findings provide very preliminary support for the idea that individuals with SAD may differ according to type attention bias, avoidant or vigilant, as these biases changed in different ways following cognitive-behavioral therapy for SAD. Further research is needed to replicate and extend these findings in order to evaluate whether SAD comprises subgroups of attentional biases.

Cross-cultural invariance of the factor structure of the Schizotypal Personality Questionnaire across Spanish and American college students.

The main goal of this study was to examine the cross-cultural invariance of the factor structure of the Schizotypal Personality Questionnaire (SPQ) (Raine, 1991) in two large samples of Spanish and American young adults. The final sample was made up of 2313 college students (508 men, 22%). Their mean age was 20.5 years (S.D.=3.2). The results indicated that the Stefanis et al. (2004) four-factor model yielded the best goodness-of-fit indices compared to alternative models. Moreover, the results support configural, metric, and partial measurement invariance of the covariances of the SPQ across the two samples. The finding of measurement equivalence across cultures provides essential evidence of construct validity for the schizotypy dimensions and of the cross-cultural validity of SPQ scores. The finding of comparable dimensional structures in cross-cultural samples lends further support to the continuum model of schizotypy and schizophrenia spectrum disorders. Future studies should continue to examine the validity of scores on the SPQ and other schizotypy measures and their variation or consistency across cultures.

Attachment anxiety moderates the relationship between childhood maltreatment and attention bias for emotion in adults

Research indicates that some individuals who were maltreated in childhood demonstrate biases in social information processing. However, the mechanisms through which these biases develop remain unclear-one possible mechanism is via attachment-related processes. Childhood maltreatment increases risk for insecure attachment. The internal working models of self and others associated with insecure attachment may impact the processing of socially relevant information, particularly emotion conveyed in facial expressions. We investigated associations among child abuse, attachment anxiety and avoidance, and attention biases for emotion in an adult population. Specifically, we examined how self-reported attachment influences the relationship between childhood abuse and attention bias for emotion. A dot probe task consisting of happy, threatening, and neutral female facial stimuli was used to assess possible biases in attention for socially relevant stimuli. Our findings indicate that attachment anxiety moderated the relationship between maltreatment and attention bias for happy emotion; among individuals with a child abuse history, attachment anxiety significantly predicted an attention bias away from happy facial stimuli.