Antonia N. Kaczkurkin

Generalized Anxiety Disorder Is Associated With Overgeneralization of Classically Conditioned Fear

BACKGROUND Meta-analytic results of fear-conditioning studies in the anxiety disorders implicate generalization of conditioned fear to stimuli resembling the conditioned danger cue as one of the more robust conditioning markers of anxiety pathology. Due to the absence of conditioning studies assessing generalization in generalized anxiety disorder (GAD), results of this meta-analysis do not reveal whether such generalization abnormalities also apply to GAD. The current study fills this gap by behaviorally and psychophysiologically assessing levels of conditioned fear generalization across adults with and without GAD. METHODS Twenty-two patients with a DSM-IV-Text Revision diagnosis of GAD and 26 healthy comparison subjects were recruited and tested. The employed generalization paradigm consisted of quasi-randomly presented rings of gradually increasing size, with extreme sizes serving as conditioned danger cues (CS+) and conditioned safety cues. The rings of intermediary size served as generalization stimuli, creating a continuum of similarity between CS+ and conditioned safety cues across which to assess response slopes, referred to as generalization gradients. Primary outcome variables included slopes for fear-potentiated startle (electromyography) and self-reported risk ratings. RESULTS Behavioral and psychophysiological findings demonstrated overgeneralization of conditioned fear among patients with GAD. Specifically, generalization gradients were abnormally shallow among GAD patients, reflecting less degradation of the conditioned fear response as the presented stimulus differentiated from the CS+. CONCLUSIONS Overgeneralization of conditioned fear to safe encounters resembling feared situations may contribute importantly to the psychopathology of GAD by proliferating anxiety cues in the individuals environment that are then capable of evoking and maintaining anxiety and worry associated with GAD.

The effect of manipulating task difficulty on error-related negativity in individuals with obsessive-compulsive symptoms

Previous research has found that individuals with obsessive-compulsive (OC) symptoms show larger error-related negativity (ERN) and correct-response negativity (CRN) amplitudes than controls. Task difficulty was manipulated during a flanker task and a probabilistic learning task to determine the effect of difficulty on ERN and CRN amplitudes in those with high or low levels of OC symptoms. Increasing task difficulty during a flanker task attenuated ERN amplitudes and enhanced CRN amplitudes. Although larger ERN amplitudes were found in the high OC group compared to the low OC group during the easy flanker task, this group difference was no longer apparent during the difficult version of the flanker task. Increasing difficulty during the probabilistic learning task had no effect on group differences in ERN or CRN amplitudes. The results of this study suggest that the hyperactive error-monitoring activity associated with OC symptoms depends on the difficulty and type of task performed.

Elevated Amygdala Perfusion Mediates Developmental Sex Differences in Trait Anxiety

BACKGROUND Adolescence is a critical period for emotional maturation and is a time when clinically significant symptoms of anxiety and depression increase, particularly in females. However, few studies relate developmental differences in symptoms of anxiety and depression to brain development. Cerebral blood flow is one brain phenotype that is known to have marked developmental sex differences. METHODS We investigated whether developmental sex differences in cerebral blood flow mediated sex differences in anxiety and depression symptoms by capitalizing on a large sample of 875 youths who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. Perfusion was quantified on a voxelwise basis using arterial spin-labeled magnetic resonance imaging at 3T. Perfusion images were related to trait and state anxiety using general additive models with penalized splines, while controlling for gray matter density on a voxelwise basis. Clusters found to be related to anxiety were evaluated for interactions with age, sex, and puberty. RESULTS Trait anxiety was associated with elevated perfusion in a network of regions including the amygdala, anterior insula, and fusiform cortex, even after accounting for prescan state anxiety. Notably, these relationships strengthened with age and the transition through puberty. Moreover, higher trait anxiety in postpubertal females was mediated by elevated perfusion of the left amygdala. CONCLUSIONS Taken together, these results demonstrate that differences in the evolution of cerebral perfusion during adolescence may be a critical element of the affective neurobiological characteristics underlying sex differences in anxiety and mood symptoms.

Generalization of Conditioned Fear and Obsessive-Compulsive Traits

Generalization of conditioned fear refers to the transfer of the conditioned fear response to stimuli that resemble the original conditioned stimulus. Overgeneralization of conditioned fear has been associated with panic disorder and generalized anxiety disorder and may be relevant to obsessive-compulsive (OC) symptoms as well. This study represents the first attempt to determine the degree to which individuals with high versus low OC traits over generalize conditioned fear. We hypothesized that the high OC individuals, particularly those characterized by overestimation of threat, would show overgeneralization of conditioned fear compared to controls as measured by behavioral and psychophysiological (fear-potentiated startle) measures. The results of this study show an interaction between the high and low Threat Estimation groups as measured by the Obsessive Beliefs Questionnaire, which suggests that those who have a tendency to overestimate threat show overgeneralization of conditioned fear. This finding suggests that the relation between OC symptoms and overgeneralization of conditioned fear may be specific to the high threat estimation component of OC symptoms.

Emotion Regulation Is Associated With PTSD and Depression Among Female Adolescent Survivors of Childhood Sexual Abuse.

Objective: Sexual abuse experienced in childhood and adolescence is associated with severity of posttraumatic stress disorder (PTSD), depressive symptoms, and emotion regulation difficulties. The current study examined the relationships among these factors in a sample of adolescents with sexual abuse-related PTSD. It was hypothesized that (a) self-perceived emotion regulation difficulties would predict severity of PTSD and depressive symptoms, and that (b) depressive symptoms would mediate the relationship between emotion regulation difficulties and PTSD. Method: Ninety treatment-seeking female adolescents with a history of sexual abuse were evaluated using the Child PTSD Symptom Scale-Interview and completed the Negative Mood Regulation Questionnaire and the Beck Depression Inventory as part of a baseline evaluation. Results: Greater emotion regulation difficulties were associated with greater severity of PTSD and depressive symptoms. In addition, the relationship between emotion regulation difficulties and PTSD severity was mediated by depressive symptoms. However, the reverse was also true: the relationship between emotion regulation difficulties and depressive symptoms was mediated by PTSD symptoms. Conclusions: Mediation analyses showed that emotion regulation difficulties were associated with both PTSD and depressive symptoms rather than fitting a unidirectional model. These findings are consistent with and extend previous research and highlight the importance of emotion regulation in adolescent survivors of sexual abuse.

The impact of treatment condition and the lagged effects of PTSD symptom severity and alcohol use on changes in alcohol craving.

Given the high rates of comorbidity between posttraumatic stress disorder (PTSD) and substance use disorder (SUD), we investigated an integrated treatment for these disorders. Individuals with comorbid PTSD and alcohol dependence were randomized to receive naltrexone or placebo, with or without prolonged exposure (PE). All participants also received BRENDA (supportive counseling). The naltrexone plus PE group showed a greater decline in alcohol craving symptoms than those in the placebo with no PE group. The PE plus placebo and the naltrexone without PE groups did not differ significantly from the placebo with no PE group in terms of alcohol craving. No treatment group differences were found for percentage of drinking days. Alcohol craving was moderated by PTSD severity, with those with higher PTSD symptoms showing faster decreases in alcohol craving. Both PTSD and alcohol use had a lagged effect on alcohol craving, with changes in PTSD symptoms and percentage of days drinking being associated with subsequent changes in craving. These results support the relationship between greater PTSD symptoms leading to greater alcohol craving and suggest that reducing PTSD symptoms may be beneficial to reducing craving in those with co-occurring PTSD/SUD.

Ethnoracial differences in PTSD symptoms and trauma-related cognitions in treatment-seeking active duty military personnel for PTSD

Objective: It is uncertain whether ethnoracial factors should be considered by clinicians assessing and treating posttraumatic stress disorder (PTSD) among service members. The purpose of this study was to shed light on ethnoracial variation in the presentation of PTSD symptoms, trauma-related cognitions, and emotions among treatment-seeking active duty military personnel. Method: Participants were 303 male active duty military members with PTSD participating in a clinical trial (60% were self-identified as White, 19% as African American, and 21% as Hispanic/Latino). In the parent study, participants completed a baseline assessment that included clinician-administered and self-report measures of PTSD, trauma-related cognitions, and emotions. Results: Multivariate hierarchical regression models were used to examine ethnoracial differences in these variables, covarying age, education, military grade, combat exposure, and exposure to other potentially traumatic events. Hispanic/Latino and African American participants reported more reexperiencing symptoms, more fear, and more guilt and numbing than White participants. All effect sizes were in the small to medium range. Conclusions: These findings suggest ethnoracial variation in PTSD symptom burden and posttraumatic cognitions among treatment-seeking service members with PTSD. Attending to cultural factors related to differences in PTSD presentation and cognitive coping strategies during the assessment and treatment process could increase rapport and lead to more comprehensive trauma processing.

Cognitive Emotion Regulation Strategies Associated With the DSM-5 Posttraumatic Stress Disorder Criteria

Maladaptive cognitive emotion regulation strategies have been proposed to contribute to the maintenance of posttraumatic stress disorder (PTSD). Prior work has focused on the relationship between these strategies and PTSD as a whole, rather than on how they are related to each PTSD symptom cluster. The purpose of the current study was to determine whether cognitive emotion regulation strategies are predictive of certain PTSD symptom clusters under the Diagnostic and Statistical Manual of Mental Disorders 5th ed. (DSM-5; American Psychiatric Association, 2013) criteria (intrusive thoughts, avoidance, negative alterations in cognitions and mood, and hyperarousal). Participants included 365 treatment-seeking, active-duty military personnel with PTSD. The negative alterations in cognitions and mood cluster were associated with dysfunctional cognitions: greater negative cognitions about the self, negative cognitions about the world, and self-blame, as well as catastrophizing (Rc2 = .519). The negative alterations in cognitions and mood cluster did not show a strong relationship with blaming others, possibly due to the complex nature of self- and other-blame in this primarily deployment-related PTSD sample. Finally, the intrusive thoughts cluster was associated with catastrophizing (Rc2 = .211), suggesting an association between frequent intrusive memories and excessively negative interpretation of those memories.

The effect of treatment on quality of life and functioning in OCD

BACKGROUND Given that obsessive compulsive disorder (OCD) is associated with impaired quality of life (QoL) and functioning, it is important examine whether therapeutic recovery from OCD leads to improvements on these important secondary outcomes. Only a few studies have examined how measures of OCD symptom severity relate to QoL and functioning among patients receiving treatment for OCD. METHODS OCD severity was measured with the Obsessive-Compulsive Inventory-Revised (OCI-R), a self-report scale of OCD, and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), an interview measure of OCD. Participants were 100 adults with a primary diagnosis of OCD on serotonin reuptake inhibitors (SRIs) enrolled in a randomized clinical trial comparing SRI augmentation with either exposure and response prevention (EX/RP) therapy, risperidone, or pill placebo. At baseline, mid-treatment, and post-treatment, patients completed assessments for OCD symptoms and QoL/functioning measures. Multilevel modeling was used to assess changes in QoL/functioning over the course of treatment and to compare such changes across treatment conditions. RESULTS Improvements in QoL/functioning were significantly greater among those receiving EX/RP compared to those receiving risperidone. Compared to pill placebo, EX/RP performed better on measures of functioning but not QoL. Greater improvement in individual OCI-R scores was associated with greater improvements in QoL/functioning, regardless of condition. In addition, Y-BOCS scores appeared to moderate improvements in QoL over the course of all treatment conditions, such that those with higher Y-BOCS scores showed the greatest improvements in QoL over time. CONCLUSIONS Improvements in QoL/functioning were associated with reduction in OCD symptom severity. The implications on OCD treatment and clinical research are discussed.

Common and dissociable regional cerebral blood flow differences associate with dimensions of psychopathology across categorical diagnoses

The high comorbidity among neuropsychiatric disorders suggests a possible common neurobiological phenotype. Resting-state regional cerebral blood flow (CBF) can be measured noninvasively with magnetic resonance imaging (MRI) and abnormalities in regional CBF are present in many neuropsychiatric disorders. Regional CBF may also provide a useful biological marker across different types of psychopathology. To investigate CBF changes common across psychiatric disorders, we capitalized upon a sample of 1042 youths (ages 11–23 years) who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. CBF at rest was quantified on a voxelwise basis using arterial spin labeled perfusion MRI at 3T. A dimensional measure of psychopathology was constructed using a bifactor model of item-level data from a psychiatric screening interview, which delineated four factors (fear, anxious-misery, psychosis and behavioral symptoms) plus a general factor: overall psychopathology. Overall psychopathology was associated with elevated perfusion in several regions including the right dorsal anterior cingulate cortex (ACC) and left rostral ACC. Furthermore, several clusters were associated with specific dimensions of psychopathology. Psychosis symptoms were related to reduced perfusion in the left frontal operculum and insula, whereas fear symptoms were associated with less perfusion in the right occipital/fusiform gyrus and left subgenual ACC. Follow-up functional connectivity analyses using resting-state functional MRI collected in the same participants revealed that overall psychopathology was associated with decreased connectivity between the dorsal ACC and bilateral caudate. Together, the results of this study demonstrate common and dissociable CBF abnormalities across neuropsychiatric disorders in youth.