Stephanie M. Gorka

The role of distress tolerance in the relationship between depressive symptoms and problematic alcohol use.

Empirical evidence and theory implicate the role of distress tolerance in the relationship between negative affect and alcohol use. However, limited research has been conducted to explore these relationships. As such, the purpose of this study was to examine whether distress tolerance moderates the relationship between current depressive symptoms and problematic alcohol use in a community sample of adults. Participants included 150 adults, primarily female, recruited from the local community. Problematic alcohol use was measured using the Alcohol Use Disorders Identification Test (AUDIT) total score, which is a composite measure of harmful and hazardous patterns of alcohol use and several current alcohol dependence symptoms. Distress tolerance was measured using a computerized behavioral distress tolerance task, the Computerized Paced Auditory Serial Addition Task (PASAT-C). Tobit regression analyses indicated a significant interaction between distress tolerance and depressive symptoms in predicting alcohol problems, such that depressive symptoms were significantly associated with problematic alcohol use among adults with low, but not high, distress tolerance. Thus, alcohol use interventions with a focus on distress tolerance skills in the context of depressive symptoms may be particularly effective.

Oxytocin Modulation of Amygdala Functional Connectivity to Fearful Faces in Generalized Social Anxiety Disorder

The neuropeptide oxytocin (OXT) is thought to attenuate anxiety by dampening amygdala reactivity to threat in individuals with generalized social anxiety disorder (GSAD). Because the brain is organized into networks of interconnected areas, it is likely that OXT impacts functional coupling between the amygdala and other socio-emotional areas of the brain. Therefore, the aim of the current study was to examine the effects of OXT on amygdala functional connectivity during the processing of fearful faces in GSAD subjects and healthy controls (HCs). In a randomized, double-blind, placebo (PBO)-controlled, within-subjects design, 18 HCs and 17 GSAD subjects performed a functional magnetic resonance imaging task designed to probe amygdala response to fearful faces following acute intranasal administration of PBO or OXT. Functional connectivity between the amygdala and the rest of the brain was compared between OXT and PBO sessions using generalized psychophysiological interaction analyses. Results indicated that within individuals with GSAD, but not HCs, OXT enhanced functional connectivity between the amygdala and the bilateral insula and middle cingulate/dorsal anterior cingulate gyrus during the processing of fearful faces. These findings suggest that OXT may have broad pro-social implications such as enhancing the integration and modulation of social responses.

Biomarkers of Threat and Reward Sensitivity Demonstrate Unique Associations With Risk for Psychopathology

Two emotional/motivational constructs that have been posited to underlie anxiety and depressive disorders are heightened sensitivity to threat and reduced sensitivity to reward, respectively. It is unclear, though, whether these constructs are only epiphenomena or also connote risk for these disorders (and relatedly, whether they connote risk for separate disorders). Using family history of psychopathology as an indicator of risk, the present study examined whether biomarkers of sensitivity to threat (startle potentiation) and reward (frontal EEG asymmetry) were associated with similar or different familial liabilities. In addition, the present study examined whether these biomarkers were associated with risk independent of proband DSM-IV diagnosis. One-hundred and seventy-three individuals diagnosed with panic disorder (PD), early onset major depressive disorder (MDD), both (comorbids), or controls completed two laboratory paradigms assessing sensitivity to predictable/unpredictable threat (measured via startle response) and reward (measured via frontal EEG asymmetry during a gambling task). Results indicated that across all participants: (a) startle potentiation to unpredictable threat was associated with family history of PD (but not MDD); and (b) frontal EEG asymmetry while anticipating reward was associated with family history of MDD (but not PD). Additionally, both measures continued to be associated with family history of psychopathology after controlling for proband DSM-IV diagnosis. Results suggest that the proposed biomarkers of sensitivity to unpredictable threat and reward exhibit discriminant validity and may add to the predictive validity of the DSM-IV defined constructs of PD and MDD, respectively.

Anterior insula responds to temporally unpredictable aversiveness: an fMRI study

A heightened sensitivity to unpredictable aversiveness is a key component of several anxiety disorders. Neuroimaging studies of unpredictable aversiveness have shown that the anterior region of the insula cortex (AIC) plays a central role in the anticipation of unpredictable aversiveness. The present study extended these findings by examining the role of the AIC in temporal unpredictability (i.e. not knowing when the stimulus will occur), a particularly critical aspect of unpredictability as it increases contextual anxiety and vigilance, given that the danger could happen ‘at any time’. Nineteen healthy participants underwent functional MRI while anticipating either temporally unpredictable or predictable aversive (or neutral) images. Participants showed greater right AIC activation while anticipating unpredictable relative to predictable aversive images. In addition, activation in this region was correlated positively with self-reported individual differences in a key facet of intolerance of uncertainty (inhibitory behavior). Taken together, the present study suggests that the AIC plays an important role in the anticipation of temporally unpredictable aversiveness and may mediate key deficits in anxiety disorders.

Neural response to reward anticipation in those with depression with and without panic disorder

BACKGROUND One of the hallmark features of major depressive disorder (MDD) is reduced reward anticipation. There have been mixed findings in the literature as to whether reward anticipation deficits in MDD are related to diminished mesolimbic activation and/or enhanced dorsal anterior cingulate activation (dACC). One of the reasons for these mixed findings is that these studies have typically not addressed the role of comorbid anxiety, a class of disorders which frequently co-occur with depression and have a common neurobiology. METHODS The aim of the current study was to examine group differences in neural responses to reward anticipation in 40 adults with either: (1) current MDD with no lifetime diagnosis of an anxiety disorder (MDD-only), (2) current MDD with comorbid panic disorder (MDD-PD), or (3) no lifetime diagnosis of psychopathology. All participants completed a passive slot machine task during a functional magnetic resonance imaging (fMRI) scan. RESULTS Analyses indicated that there were no group differences in activation of mesolimbic reward regions; however, the MDD-only group exhibited greater dACC activation during the anticipation of rewards compared with the healthy controls and the comorbid MDD-PD group (who did not differ from each other). LIMITATIONS The sample size was small which limits generalizability. CONCLUSIONS These findings provide preliminary support for the role of hyperactive dACC functioning in reduced reward anticipation in MDD. They also indicate that comorbid anxiety may alter the association between MDD and neural responding to reward anticipation.

Startle response to unpredictable threat in comorbid panic disorder and alcohol dependence

BACKGROUND Although the adverse consequences of comorbid panic disorder (PD) and alcohol dependence (AD) are well-established, relatively little is known about the mechanisms underlying their co-occurrence. Several researchers have postulated that alcohols ability to dampen response to unpredictable threat may be an important motivational factor in comorbid PD and AD. To date, no research has examined these processes using a clinical sample and it is unclear whether individuals with PD and AD evidence different reactivity to unpredictable threat relative to individuals with PD-only. METHODS The aim of the current study was to examine differences in aversive responding during predictable and unpredictable threat-of-shock in three groups of individuals with: (1) current PD and remitted AD (PD and AD), (2) current PD but no lifetime diagnosis of AD (PD-only), and (3) no lifetime diagnoses of PD or AD (controls). Aversive responding was assessed using a well-established electromyography (EMG) startle paradigm. RESULTS Results indicated that PD and AD individuals evidenced greater startle potentiation during unpredictable (but not predictable) threat relative to controls and PD-only individuals (who did not differ). CONCLUSIONS These findings suggest that heightened reactivity to unpredictable threat may be an important process in PD and AD comorbidity and a possible key motivational factor underlying engagement in alcohol use.

Association between problematic alcohol use and reactivity to uncertain threat in two independent samples.

BACKGROUND Recent laboratory studies have shown that acute alcohol intoxication selectively and effectively dampens aversive responding to uncertain threat. An emerging hypothesis is that individuals who exhibit heightened reactivity to uncertain threat may be especially motivated to use alcohol to dampen their distress, setting the stage for negative reinforcement processes to drive excessive alcohol use. However, no study to date has directly examined whether current problematic drinkers exhibit heightened reactivity to uncertain threat as would be expected. METHODS The present study was therefore designed to examine the association between current problematic alcohol use and reactivity to uncertain threat during sobriety in two, independent samples. In Study 1 (n=221) and Study 2 (n=74), adult participants completed the same well-validated threat-of-shock task which separately probes responses to temporally predictable and unpredictable threat. Startle potentiation was measured as an index of aversive responding. Problematic alcohol use was defined as number of binge episodes within the past 30days in Study 1 and total scores on a self-report measure of hazardous drinking in Study 2. RESULTS As hypothesized, across both studies greater levels of problematic drinking were associated with greater startle potentiation to unpredictable threat. In Study 2, hazardous drinking scores were also positively associated with startle potentiation to predictable threat. CONCLUSIONS The findings are notably consistent with the notion that heightened reactivity to uncertain threat is an important individual difference factor associated with the onset and/or maintenance of problematic drinking behaviors and may therefore be a novel prevention and intervention target.

Startle Potentiation to Uncertain Threat as a Psychophysiological Indicator of Fear-Based Psychopathology: An Examination Across Multiple Internalizing Disorders

Heightened reactivity to uncertain threat (U-threat) is an important individual difference factor that may characterize fear-based internalizing psychopathologies (IPs) and distinguish them from distress/misery IPs. To date, however, the majority of existing research examining reactivity to U-threat has been within individuals with panic disorder and major depressive disorder (MDD) and no prior study has directly tested this hypothesis across multiple IPs. The current study therefore explored whether heightened reactivity to U-threat is a psychophysiological indicator of fear-based psychopathology across 5 groups: current (a) social anxiety disorder (SAD); (b) specific phobia (SP); (c) generalized anxiety disorder (GAD); (d) MDD; and (c) individuals with no history of psychopathology (controls). All 160 adults completed a well-validated threat-of-shock task designed to probe responses to predictable (P-) and U-threat. Startle eyeblink potentiation was recorded as an index of aversive arousal. Results indicated that individuals with SAD and SP evidenced greater startle potentiation to U-threat, but not P-threat, relative to individuals with GAD, MDD, and controls (who did not differ). The current findings, along with the prior panic disorder and MDD literature, suggest that heightened reactivity to U-threat is a psychophysiological indicator of fear-based disorders and could represent a neurobiological organizing principle for internalizing psychopathology. The findings also suggest that individuals with fear disorders generally display a hypersensitivity to uncertain aversive events, which could contribute to their psychopathology.

Cannabinoid Modulation of Amygdala Subregion Functional Connectivity to Social Signals of Threat

Background: Δ9-Tetrahydrocannabinol has been shown to modulate anxiety and facilitate the extinction of fear by inhibiting amygdala reactivity. Since functional coupling between the amygdala and prefrontal cortex is implicated in affective processes, it is possible that Δ9-tetrahydrocannabinol affects amygdala-prefrontal cortex functional connectivity in ways that differ across amygdala subregions: basolateral, centromedial, and superficial. Methods: The aim of the study was to examine the effects of Δ9-tetrahydrocannabinol on functional connectivity between amygdala subregions and the prefrontal cortex during socio-emotional threat in healthy adults using a double-blind, placebo-controlled, within-subjects design. Sixteen subjects completed a functional magnetic resonance imaging task designed to probe amygdala responses to social threat. Amygdala subregion-prefrontal cortex functional connectivity was compared between Δ9-tetrahydrocannabinol and placebo using generalized psychophysiological interaction analyses. Results: Findings indicated that Δ9-tetrahydrocannabinol enhanced basolateral and superficial amygdala connectivity to the rostral anterior cingulate/medial prefrontal cortex. Conclusion: These effects, including Δ9-tetrahydrocannabinol’s potential ability to reduce threat perception or enhance socio-emotional regulation, may help understand the neurocircuitry of affect.

Aversive responding to safety signals in panic disorder: The moderating role of intolerance of uncertainty

An inability to inhibit aversive responding during conditions that signal safety may be a core dysfunction associated with anxiety disorders. However, there has been inconsistent evidence as to whether individuals with panic disorder (PD) exhibit aversive responding during safety signals. It is therefore possible that only certain subgroups of PD patients, particularly those with high levels of intolerance of uncertainty (IU), evidence this type of abnormal responding. The aim of the current study was to examine whether IU moderates the association between PD and startle potentiation during (a) safety and (b) threat periods during a threat-of-shock task. Participants included 172 adults, 74 of which had current diagnoses of PD. Results indicated that at high levels of IU, PD was associated with greater startle potentiation during safety. At low levels of IU, PD was not associated with startle potentiation during safety. IU did not moderate the effect of PD on threat responding. These results suggest that PD patients with high levels of IU fail to inhibit aversive responding during safety, possibly due to a tendency to interpret distal threat as distressing.