Heightened sensitivity to threat and reduced sensitivity to reward are potential mechanisms of dysfunction in anxiety and depressive disorders, respectively. However, few studies have simultaneously examined whether these mechanisms are unique or common to these disorders. In this study, sensitivity to predictable and unpredictable threat (measured by startle response during threat anticipation) and sensitivity to reward (measured by frontal electroencephalographic [EEG] asymmetry during reward anticipation) were assessed in 4 groups (N = 191): those with (1) panic disorder (PD) without a lifetime history of depression, (2) major depression (MDD) without a lifetime history of an anxiety disorder, (3) comorbid PD and MDD, and (4) controls. General distress/negative temperament (NT) was also assessed via self-report. Results indicated that PD (with or without comorbid MDD) was uniquely associated with heightened startle to predictable and unpredictable threat, and MDD (with or without comorbid PD) was uniquely associated with reduced frontal EEG asymmetry. Both psychophysiological measures of threat and reward sensitivity were stable on retest approximately 9 days later in a subsample of participants. Whereas the comorbid group did not respond differently on the tasks relative to the PD-only and MDD-only groups, they did report greater NT than these 2 groups (which did not differ from each other). Results suggest that heightened sensitivity to threat and reduced sensitivity to reward may be specific components of PD and MDD, respectively. In addition, relative to noncomorbid depression and PD, comorbid MDD and PD may be characterized by heightened NT, but not abnormal levels of these “specific” components.

Distress intolerance may be an important individual difference variable in understanding maladaptive coping responses across diagnostic categories. However, the measurement of distress intolerance remains inconsistent across studies and little evidence for convergent validity among existing measures is available. This study evaluated the overlap among self-report and behavioral measures of distress intolerance in four samples, including an unselected sample, a sample of patients with drug dependence, and two samples of cigarette smokers. Results suggested that the self-report measures were highly correlated, as were the behavioral measures; however, behavioral and self-report measures did not exhibit significant associations with each other. There was some evidence of domain specificity, with anxiety sensitivity demonstrating strong associations with somatic distress intolerance, and a lack of association between behavioral measures that elicit affective distress and those that elicit somatic distress. These findings highlight a potential divergence in the literature relative to the conceptualization of distress intolerance as either sensitivity to distress or as the inability to persist at a task when distressed. Further research is needed to elucidate the conceptualization and measurement of distress intolerance to facilitate future clinical and research applications of this construct.

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 five groups: current 1) social anxiety disorder (SAD), 2) specific phobia (SP), 3) generalized anxiety disorder (GAD), 4) MDD, and 5) 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.

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.

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 exploring these relationships. As such, the purpose of the current 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.

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 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: 1) startle potentiation to unpredictable threat was associated with family history of PD (but not MDD) and 2) 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.

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 magnetic resonance imaging while anticipating either temporally unpredictable or predictable aversive (or neutral) images. Participants exhibited greater right AIC while anticipating unpredictable relative to predictable aversive images. Additionally, activation in this region was positively correlated 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.

Effective, parsimonious behavioral interventions that target reinforcement are needed for substance users with depression to improve mood as well as treatment retention. The Life Enhancement Treatment for Substance Use (LETS ACT; Daughters et al., 2008) is a behavioral activation-based approach tailored to increase levels of positive reinforcement among depressed substance users while in substance abuse treatment. The current study tested the efficacy of LETS ACT compared to a contact-time matched control condition, supportive counseling (SC), examining effects on depressed mood, substance abuse treatment retention, and behavioral activation outcomes. Fifty-eight adult substance users in residential substance abuse treatment presenting with depressive symptoms (BDI ≥ 12) were randomly assigned to LETS ACT or SC. Assessments were administered at pre- and post-treatment and included assessment of DSM-IV psychiatric diagnoses, depression severity, treatment motivation, overall activation, environmental reward, and substance abuse treatment retention. Patients in LETS ACT had significantly higher rates of substance abuse treatment retention and significantly greater increases in activation on the Behavioral Activation for Depression Scale (BADS) compared to those in SC. Both groups had decreased depression severity at post-treatment, although the group by time interaction was not significant. This study was the first to compare LETS ACT to a contact-time matched control treatment to evaluate effects on substance abuse treatment retention and two distinct measures of behavioral activation: overall activation and environmental reward. Findings suggest preliminary support for the feasibility, tolerability, and efficacy of a brief behavioral activation-based protocol that may be particularly useful to improve substance abuse treatment retention.