Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving symptoms of SAD. In the present study, we conducted secondary analyses on data from a randomized clinical trial to determine whether C-reactive protein (CRP) concentrations and social anxiety symptoms decreased over the course of virtual reality exposure therapy, and whether changes in social anxiety symptoms as a function of treatment varied as a function of CRP. METHOD: Adult participants (N = 78) with a diagnosis of SAD (59 % female) were randomized to receive exposure therapy alone, or exposure therapy supplemented with scopolamine. Social anxiety symptoms, salivary CRP, and subjective units of distress were measured across three exposure therapy sessions, at a post-treatment extinction retest, and at a 1-month follow-up. RESULTS: CRP decreased over the course of treatment, b = -0.03 (SE = 0.01), p =.02 95 %CI [-0.06, -0.004], as did all social anxiety symptom domains and subjective distress. Higher CRP was associated with greater decreases from pre-treatment to 1-month follow-up in fear, b = -0.45 (SE = 0.15), p =.004 95 %CI [-0.74, -0.15], and avoidance, b = -0.62 (SE = 0.19), p =.002 95 %CI [-1.01, -0.23], and in-session subjective distress from pre-treatment to post-treatment, b = -0.42 (SE = 0.21), p =.05 95 %CI [-0.83, -0.001]. However, declines in CRP were not correlated with declines in fear, r = -0.07, p =.61, or avoidance, r = -0.10, p =.49, within-persons. CONCLUSIONS: Virtual reality exposure therapy may be associated with an improvement in systemic inflammation in patients with severe SAD. Pre-treatment CRP may also be of value in predicting which patients stand to benefit the most from this treatment.

Changes in positive and negative affect in psychotherapy for depression and anxiety.

OBJECTIVE: Positive and negative affect play critical roles in depression and anxiety treatment, but the dynamic processes of how affect changes over treatment in relation to changes in symptoms is unclear. The study goal was to examine relationships among changes in positive and negative affect with changes in depression and anxiety symptoms. METHOD: This secondary analysis used a combined sample (N = 196) of two trials (Craske et al., 2019, 2023) comparing positive affect treatment (PAT) to negative affect treatment. Longitudinal cross-lag panel models explored whether changes in positive and negative affect (Positive and Negative Affect Schedule; Watson et al., 1988) predicted subsequent changes in depression and anxiety symptoms (Depression Anxiety Stress Scales; Lovibond & Lovibond, 1995), whether symptoms predicted subsequent changes in affect, and whether treatment condition moderated these relationships. RESULTS: Increases in positive affect predicted subsequent decreases in depression and anxiety symptoms, regardless of treatment condition. Symptoms did not reciprocally predict changes in positive affect. For individuals in PAT, decreases in negative affect predicted subsequent decreases in symptoms. Moreover, decreases in symptoms predicted subsequent decreases in negative affect, regardless of treatment condition. CONCLUSIONS: Results did not support a reciprocal relationship between positive affect and symptoms of depression and anxiety since positive affect predicted depression and anxiety symptoms but not vice versa. Results supported a reciprocal relationship between negative affect and symptoms of depression and anxiety since negative affect predicted depression and anxiety symptoms in PAT, and depression and anxiety symptoms predicted negative affect in both treatment conditions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Does fear reduction predict treatment response to exposure for social anxiety disorder?

BACKGROUND AND OBJECTIVES: Fear activation and reduction have traditionally been considered important mechanisms of exposure therapy. Evidence to date is mixed and impeded by inadequate methodology. This study examined the extent to which fear activation and reduction within and across exposures predicted treatment outcomes for social anxiety disorder within a paradigm suitable for their measurement. METHODS: Sixty-eight adults with social anxiety disorder and fear of public speaking completed seven exposure sessions, each consisting of seven speeches conducted in virtual reality. Exposures were identical in duration, task requirements, and virtual public speaking situation. Fear was measured with skin conductance and subjective distress ratings. At baseline and post-treatment, participants completed a public speaking behavioral approach test with a panel of confederate judges; subjective fear was measured. A standardized questionnaire of anxiety symptoms was administered at baseline, post-treatment, and one-month follow-up. RESULTS: No indices of within- or between-session fear reduction, measured by subjective distress and skin conductance response, predicted treatment outcome. One measure of fear activation was associated with outcomes such that less activation predicted greater symptom reduction; remaining indices did not predict outcomes. LIMITATIONS: Data were collected in the context of a randomized controlled trial of scopolamine; drug group was included in analytic models to account for drug influence. VR exposures elicited mild levels of distress that may underestimate levels of distress in clinical settings. CONCLUSIONS: Findings failed to support fear activation or reduction within or across exposure sessions as significant predictors of treatment outcome for social anxiety. Treatment implications are discussed.

Optimizing exposure therapy with an inhibitory retrieval approach and the OptEx Nexus.

Research from recent decades has highlighted the distinction between excitatory and inhibitory Pavlovian learning mechanisms. Based on this distinction, state-of-the-art exposure therapy for anxiety disorders emphasizes inhibitory learning and retrieval as its primary mechanism for long-term reduction in fear, anxiety, and avoidance. Seven years ago, we (Craske, et al., 2014) summarized exposure therapy from an inhibitory learning approach, focusing on eight exposure optimization strategies. Here, we update this model based on recent work and describe how to conduct exposure therapy from an inhibitory retrieval approach and encourage further empirical investigation of its basic premises. To this end, we guide the reader in the use of the OptEx Nexus: a clinician's tool for conducting exposure therapy from an inhibitory retrieval approach. We categorize exposure strategies as fundamental (expectancy violation, attention to feared stimulus/situation, removal of safety signals, and mental rehearsal after exposure), advanced (deepened extinction, occasional reinforced extinction), and promoting generalization of learning (retrieval cues, multiple contexts, stimulus variability, positive affect). We additionally discuss extinction learning with distal future feared outcomes, the role of avoidance, and alternative models/approaches to exposure therapy, including counterconditioning, novelty-enhanced extinction, latent cause models, and reconsolidation. Lastly, we illustrate clinical implementation via vignettes of exposure therapy from an inhibitory retrieval approach (see Supplemental materials).

Pre-treatment hippocampal functioning impacts context renewal for cholinergic modulated exposure therapy.

Our recent trial demonstrated individuals suffering from social anxiety with performance-related concerns who received virtual reality exposure augmented with scopolamine, a cholinergic antagonist, experienced significantly less post-treatment context renewal (CX) than placebo (Craske et al., 2019). The purpose of the present investigation was to determine who specifically benefits from scopolamine by examining hippocampal (HPC) functioning as a moderator of treatment response (Placebo n = 15, SCOP 0.5 mg n = 15, SCOP 0.6 mg n = 15). Skin conductance response to conditional stimulus (SCR-to-CS) termination suggested a dose-response relationship for enhanced HPC functioning individuals, wherein individuals receiving scopolamine demonstrated less fear at CX. In addition, SCR-to-CS onset indicated reduced fear at CX for impaired HPC individuals receiving SCOP 0.5 mg and SCOP 0.6 mg relative to Placebo. Our findings, however, lacked consistency across measures. Scopolamine remains a promising agent and additional research required to further understand its effects.

Knowledge and competency standards for specialized cognitive behavior therapy for adult obsessive-compulsive disorder.

Obsessive-Compulsive Disorder (OCD) is a leading cause of disability world-wide (World Health Organization, 2008). Treatment of OCD is a specialized field whose aim is recovery from illness for as many patients as possible. The evidence-based psychotherapeutic treatment for OCD is specialized cognitive behavior therapy (CBT, NICE, 2005, Koran and Simpson, 2013). However, these treatments are not accessible to many sufferers around the world. Currently available guidelines for care are deemed to be essential but insufficient because of highly variable clinician knowledge and competencies specific to OCD. The phase two mandate of the 14 nation International OCD Accreditation Task Force (ATF) created by the Canadian Institute for Obsessive Compulsive Disorders is development of knowledge and competency standards for specialized treatments for OCD through the lifespan deemed by experts to be foundational to transformative change in this field. This paper presents knowledge and competency standards for specialized CBT for adult OCD developed to inform, advance, and offer a model for clinical practice and training for OCD. During upcoming ATF phases three and four criteria and processes for training in specialized treatments for OCD through the lifespan for certification (individuals) and accreditation (sites) will be developed based on the ATF standards.

Pavlovian Learning Processes in Pediatric Anxiety Disorders: A Critical Review.

Deficits in associative and Pavlovian learning are thought to lie at the center of anxiety-related disorders. However, the majority of studies have been carried out in adult populations. The aim of this review was to critically examine the behavioral and neuroimaging literature on Pavlovian learning in pediatric anxiety disorders. We conclude that although there is evidence for deficits in Pavlovian processes (e.g., heightened reactivity to safety cues in anxious samples), the extant literature suffers from key methodological and theoretical issues. We conclude with theoretical and methodological recommendations for future research in order to further elucidate the role of Pavlovian learning in the etiology, maintenance, and treatment of pediatric anxiety disorders.

Measuring fear: Association among different measures of fear learning.

BACKGROUND AND OBJECTIVES: Fear conditioning paradigms use various measures to assess learned fear, including autonomic arousal responses like skin conductance, and self-reports of both associative (US-expectancies) and evaluative (affective ratings) learning. The present study uses a dimensional approach to examine associations among fear indices directly. METHODS: Seventy-three participants completed a differential fear conditioning experiment, during which a neutral stimulus (CS+) was paired with an electric shock (US), while another stimulus (CS-) was never paired with the shock (partially instructed fear acquisition). Ten minutes later, both stimuli were presented without any shocks (fear extinction). Skin conductance responses and US-expectancy ratings were recorded during each phase, while self-reported negative affect was assessed for each CS at the end of extinction. RESULTS: Results showed a positive association among US-expectancy ratings and skin conductance responses during acquisition and early extinction. US-expectancy ratings during overall extinction were positively associated with post-extinction negative affect. LIMITATIONS: The lack of affective ratings post-acquisition may have obscured associations between associative and evaluative learning indices. CONCLUSIONS: Results provide evidence for the expected correspondence among different indices of associative fear learning. Findings emphasize the need for incorporating both associative and evaluative learning measures in fear conditioning paradigms.

Endogenous in-session cortisol during exposure therapy predicts symptom improvement: Preliminary results from a scopolamine-augmentation trial.

The purpose of this study was to explore whether individual differences in glucocorticoid concentrations were associated with symptom improvement following exposure therapy for patients with social anxiety disorder. To do this, 60 participants with social anxiety disorder completed a randomized-controlled trial of exposure therapy, where participants were randomized to receive scopolamine-augmentation or placebo during their 7 exposure sessions. Scopolamine is an antimuscarinic which blocks the effects of acetylcholine and reduces autonomic arousal. During sessions 1, 4, 7, and during the post-treatment extinction assessment, participants provided up to 16 saliva samples (4 in each session). Pre-treatment, post-treatment, and at 1-month follow-up, participants completed the Liebowitz Social Anxiety Scale to monitor change in fear and avoidance symptoms. Elevated endogenous in-session cortisol during exposure sessions was associated with less symptom improvement from pre- to post-treatment and at 1-month follow-up. The association between elevated endogenous in-session cortisol and attenuated symptom change was not moderated by scopolamine treatment condition. Individuals with social anxiety disorder who have elevated neuroendocrine signaling may under-benefit from exposure therapy. This is the first study, to our knowledge, to examine whether endogenous in-session cortisol concentrations predict symptom changes following exposure therapy for the treatment of social anxiety disorder. More investigation of non-invasive and reliable biological markers that explain variability in responses to effective treatments are needed.

Stress-induced cortisol reactivity as a predictor of success in treatment for affective dimensions.

BACKGROUND: Response rates to first-line treatments for depression and anxiety remain unsatisfactory. Identification of predictors or moderators that can optimize treatment matching is of scientific and clinical interest. This study examined the role of prolonged laboratory-induced stress cortisol reactivity as a predictor of outcome for a treatment of affective dimensions (TAD). Patients received 15-sessions of a treatment targeting reductions in negative affect or increases in positive affect (Craske et al., 2019). A second aim was to examine whether treatment type would moderate the association between cortisol reactivity and treatment outcome. METHODS: Thirty-five participants underwent a 36-minute intermittent stress induction task composed of a mental arithmetic task and a fear-potentiated startle task one week before treatment initiation. Cortisol was collected at five-time points with reactivity being quantified as peak during the task minus basal level of cortisol the evening before the assessment. Using multilevel modeling, we examined the associations between cortisol reactivity and slopes of symptom improvement. RESULTS: Cortisol reactivity was related to treatment outcome, with average and higher levels of stress-induced cortisol response predicting greater decreases in symptoms throughout treatment and 6-month follow-up. Treatment condition differences (moderation) were not observed in the effect of cortisol reactivity on symptoms. CONCLUSION: Our findings demonstrate the impact of greater cortisol stress reactivity on treatment outcome. Future studies should investigate how to enhance this therapeutic benefit through capitalizing on endogenous diurnal fluctuations or exogenous cortisol manipulation.

Virtual Reality Reward Training for Anhedonia: A Pilot Study.

Anhedonia is a risk factor for suicide and poor treatment response in depressed individuals. Most evidence-based psychological therapies target symptoms of heightened negative affect (e.g., negative inferential style) instead of deficits in positive affect (e.g., attenuated reward response) and typically show little benefit for anhedonia. Viewing positive scenes through virtual reality (VR) has been shown to increase positive affect and holds great promise for addressing anhedonic symptoms. In this pilot study, six participants with clinically significant depression completed 13 sessions of exposure to positive scenes in a controlled VR environment. Significant decreases were found in self-reported anhedonia, depression, anxiety, and impairments in functioning from baseline to 1-month follow-up. Negative affect decreased over all 13 sessions, and positive affect increased over sessions 8-13. Results suggest that positive experiences in VR may be a novel avenue for the treatment of anhedonia in depressed individuals.

An Evidence-Based Model for Disseminating-Implementing Coordinated Anxiety Learning and Management in Department of Veterans Affairs' Community-Based Outpatient Clinics.

PURPOSE: To explore the feasibility and utility of using a workshop, and supervision-consultation plus external facilitation to disseminate and implement cognitive-behavioral therapy in Veterans Affairs (VA) community-based outpatient clinics (CBOCs). METHODS: This study occurred in the context of a randomized controlled trial aimed at comparing 2 methods for implementing Coordinated Anxiety Learning Management (CALM) in VA CBOCs. A 3-phase (workshop, supervision-consultation, external facilitation) model was used to support 32 VA CBOC mental health providers in learning and adopting CALM in their clinical practice. Qualitative data describe training activities and the feasibility and utility of each training phase in addressing challenges to adopting CALM. FINDINGS: All 3 phases of the model were feasible to use with our sample of CBOC mental health providers. Providers reported challenges learning CALM during the workshop and concerns about not having enough training post-workshop to use CALM in practice. Providers primarily utilized supervision-consultation to tailor CALM to their practice, including learning how to prioritize a target disorder, "switch" the focus of treatment to a different disorder when comorbidities were present, and modify CALM sessions to fit shorter treatment visits. Providers primarily utilized external facilitation to further tailor CALM to their practice through implementation (eg, concrete help) and support-oriented help. Key lessons for implementing CALM in CBOCs are presented and discussed. CONCLUSIONS: Findings provide initial evidence for the feasibility and utility of using each component of a facilitation-enhanced training model to promote CBOC VA providers' implementation of a computer and manual version of CALM in their practice.

Cholinergic Modulation of Exposure Disrupts Hippocampal Processes and Augments Extinction: Proof-of-Concept Study With Social Anxiety Disorder.

BACKGROUND: In rodents, context specificity of Pavlovian extinction is attenuated by manipulations that impair hippocampal function, including systemic administration of scopolamine, a muscarinic-cholinergic receptor antagonist. Context renewal translates into return of fear following exposure therapy to feared situations. We evaluated the effectiveness of scopolamine for attenuating context renewal of phobic fear in humans. METHODS: A total of 60 participants (35 female, 22 male, 1 transgender, 2 undeclared) with social anxiety disorder and fear of public speaking were randomized to placebo, 0.5 mg scopolamine, or 0.6 mg scopolamine. They completed seven exposure sessions in an exposure context and subsequently tested in the exposure context (extinction retest) versus a different context (context renewal test), which were counterbalanced. Testing 1 month later occurred in the exposure context (long-term extinction retest). Fear measures included skin conductance and self-reported distress during speeches. Hippocampus-dependent cognitive tasks were completed as well. RESULTS: Scopolamine augmented extinction across exposure sessions on skin conductance response and skin conductance level. Lower skin conductance response at context renewal in scopolamine groups relative to the placebo group was constrained to simple effects and complicated by unexpected outcomes within placebo and on self-reported fear. Scopolamine led to lower skin conductance response at long-term extinction retest. Scopolamine impaired performance on a cognitive task of hippocampal function. CONCLUSIONS: Noninvasive and well-tolerated scopolamine impaired hippocampal processes and augmented extinction during exposure. Drug-free effects persisted 1 month later. Findings at context renewal were limited and suggestive only. Further investigation is warranted with varying scopolamine dosages.

Positive affect treatment for depression and anxiety: A randomized clinical trial for a core feature of anhedonia.

OBJECTIVE: Loss of pleasure or interest in activities (i.e., anhedonia) is a risk factor for suicidality, treatment nonresponse, and relapse. Extant treatments that focus on reducing negative affect have limited effects upon positive affect (a core feature of anhedonia). We investigated whether a novel intervention aimed at increasing reward sensitivity was more efficacious for positive affect than a cognitive-behavior treatment aimed at reducing threat sensitivity, in individuals with clinically severe symptoms of depression or anxiety, and functional impairment. METHOD: The Treatment for Affective Dimensions trial was offered in a 2-site randomized study at outpatient treatment centers in Los Angeles and Dallas. Ninety-six patients were randomized to 15 weekly, individual sessions of Positive Affect Treatment (PAT) or Negative Affect Treatment (NAT). The primary outcome was improvement in positive affect (Positive and Negative Affect Schedule-Positive) from pretreatment to 6-month follow-up (6MFU). Secondary outcomes were improvements in negative affect (Positive and Negative Affect Schedule-Negative), suicidal ideation, and symptoms (Depression Anxiety Stress Scales). RESULTS: PAT resulted in greater improvements in positive affect, p = .009, d = .52, and higher positive affect at 6MFU, p = .002, d = .67, than NAT. Participants in PAT also reported lower negative affect, p = .033, d = .52, and lower symptoms of depression, p = .035, d = .34, anxiety, p < .018, d = .30, and stress, p = .006, d = .43 at 6MFU. Finally, probability of suicidal ideation at 6MFU was lower in PAT than NAT (1.7% vs. 12.0%), p < .001. CONCLUSIONS: Compared to NAT, PAT demonstrated better outcomes (at 6MFU) on positive affect, depression, anxiety, stress, and suicidal ideation, for patients with symptomatic pretreatment levels of these outcomes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Pilot for novel context generalization paradigm.

BACKGROUND AND OBJECTIVES: Following an aversive experience, fears often generalize across contexts. Contextual fear generalization is modeled in a laboratory paradigm in which one context (CTX+) is paired with an aversive unconditional stimulus (US), while the other context (CTX-) is not. The current study sought to validate a novel paradigm assessing contextual fear generalization, and to determine the extent to which stress and anxiety symptoms enhanced contextual fear generalization. METHODS: Fifty-nine participants were randomized to a stress induction or control arithmetic test, followed by a differential context fear conditioning paradigm. One to three days later, participants completed a generalization gradient test with CTX+, CTX, and four generalization contexts. RESULTS: We found successful contextual fear conditioning on measures of US expectancy, self-report fear and valence, and startle reflex, and linear generalization across the contextual gradient on expectancies and self-report measures. Acute stress induction impaired learning of the US-CTX + association during context fear acquisition. Anxiety significantly predicted greater contextual fear generalization as measured by US expectancy. LIMITATIONS: Our study provides pilot data introducing a novel fear conditioning paradigm to assess contextual generalization of fear. There is a need for further replication to validate its utility. CONCLUSIONS: Findings suggest that individuals high in anxiety show greater contextual fear generalization as measured by US expectancy. Results are discussed in terms of potential mechanisms that contribute to pervasive anxiety.

The role of associative fear and avoidance learning in anxiety disorders: Gaps and directions for future research.

Anxiety disorders are the most common mental disorders and are often chronic and disabling. Although exposure-based treatments are effective, a substantial number of individuals fail to fully remit or experience a return of symptoms after treatment. Understanding the critical processes underlying the development and treatment of anxiety disorders will help identify individuals at risk and optimize treatments. Aversive associative learning offers explanatory pathways through which fear and anxiety emerge, spread, persist, and resurge. This narrative review examines the advances made in our understanding of associative fear and avoidance learning in anxiety disorders. Overall, the extant literature supports a key role of aversive associative learning in the development and treatment of anxiety disorders. However, research targeting specific mechanisms such as extinction generalization and avoidance, the fragility of extinction, and moderating influences of individual differences pertinent to anxiety disorders (e.g., age, sex, depression) is needed. We discuss the need for more ecological valid and complex paradigms to model ambiguity and conflict as well as for clinical translation studies to optimize treatment.

Discrimination between safe and unsafe stimuli mediates the relationship between trait anxiety and return of fear.

Individuals with anxiety disorders show deficits in the discrimination between a cue that predicts an aversive outcome and a safe stimulus that predicts the absence of that outcome. This impairment has been linked to increased spontaneous recovery of fear following extinction, however it is unknown if there is a link between discrimination and return of fear in a novel context (i.e. context renewal). It is also unknown if impaired discrimination mediates the relationship between trait anxiety and either spontaneous recovery or context renewal. The present study used a differential fear conditioning paradigm to examine the relationships between trait anxiety, discrimination learning, spontaneous recovery and context renewal in healthy volunteers. Fear learning was assessed using continuous ratings of US expectancy and subjective ratings of fear. Discrimination mediated the relationships between trait anxiety and both spontaneous recovery and context renewal such that elevated trait anxiety was associated with poorer discrimination, which in turn was associated with increased fear at test phases. Results are discussed in terms of the genesis and maintenance of anxiety disorders.

Treatment of avoidance behavior as an adjunct to exposure therapy: Insights from modern learning theory.

Pathological avoidance of benign stimuli is a hallmark of anxiety and related disorders, and exposure-based treatments have often encouraged the removal of avoidance, or safety behaviors, due to their negative effects on extinction learning. Unfortunately, empirical evidence suggests that avoidance behaviors can persist following treatment, and the mere availability of avoidance behavior can be sufficient to renew fear following successful extinction learning. The present paper critically examines the function of avoidance behavior through the lens of modern learning theory, and speculates on novel behavioral and pharmacological strategies for targeting avoidance as an adjunct to current evidence-based treatments.

Can Memories of Traumatic Experiences or Addiction Be Erased or Modified? A Critical Review of Research on the Disruption of Memory Reconsolidation and Its Applications.

Recent research suggests that the mere act of retrieving a memory can temporarily make that memory vulnerable to disruption. This process of "reconsolidation" will typically restabilize the neural representation of the memory and foster its long-term storage. However, the process of reconsolidating the memory takes time to complete, and during this limited time window, the original memory may be modified either by the presentation of new information or with pharmacological agents. Such findings have prompted rising interest in using disruption during reconsolidation as a clinical intervention for anxiety, posttraumatic stress, and substance use disorders. However, "boundary conditions" on memory reconsolidation may pose significant obstacles to clinical translation. The aim of this article is to critically examine the nature of these boundary conditions, their neurobiological substrates, and the potential effect they may have on disruption of reconsolidation as a clinical intervention. These boundary conditions also highlight potential constraints on the reconsolidation phenomenon and suggest a limited role for memory updating consistent with evolutionary accounts of associative learning for threat and reward. We conclude with suggestions for future research needed to elucidate the precise conditions under which reconsolidation disruption may be clinically useful.

Treatment for Anhedonia: A Neuroscience Driven Approach.

Anhedonia, or loss of interest or pleasure in usual activities, is characteristic of depression, some types of anxiety, as well as substance abuse and schizophrenia. Anhedonia is a predictor of poor long-term outcomes, including suicide, and poor treatment response. Because extant psychological and pharmacological treatments are relatively ineffective for anhedonia, there is an unmet therapeutic need for this high-risk symptom. Current psychological and drug treatments for anxiety and depression focus largely on reducing excesses in negative affect rather than improving deficits in positive affect. Recent advances in affective neuroscience posit that anhedonia is associated with deficits in the appetitive reward system, specifically the anticipation, consumption, and learning of reward. In this paper, we review the evidence for positive affect as a symptom cluster, and its neural underpinnings, and introduce a novel psychological treatment for anxiety and depression that targets appetitive responding. First, we review anhedonia in relation to positive and negative valence systems and current treatment approaches. Second, we discuss the evidence linking anhedonia to biological, experiential, and behavioral deficits in the reward subsystems. Third, we describe the therapeutic approach for Positive Affect Treatment (PAT), an intervention designed to specifically target deficits in reward sensitivity.