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Anhedonia is a core symptom of major depressive disorder (MDD) resulting from maladaptive reward processing. Electroconvulsive therapy (ECT) is an effective treatment for patients with MDD. No previous neuroimaging studies have taken a dimensional approach to assess whether ECT-induced volume changes are specifically related to improvements in anhedonia and positive valence emotional constructs. We aimed to assess the relationship between ECT-induced brain volumetric changes and improvement in anhedonia and reward processing in patients with MDD.We evaluated 15 patients with MDD before and after ECT. We used magnetic resonance imaging, clinical scales (i.e., Quick Inventory of Depressive Symptomatology for syndromal depression severity and Snaith-Hamilton Pleasure Scale for anhedonia) and the Temporal Experience of Pleasure Scale for anticipatory and consummatory experiences of pleasure. We identified 5 regions of interest within the reward circuit and a 6th control region relevant for MDD but not core to the reward system (Brodmann Area 25).Anhedonia, anticipatory and consummatory reward processing improved after ECT. Volume increases within the right reward system separated anhedonia responders and non-responders. Improvement in anticipatory (but not consummatory) reward correlated with increases in volume in hippocampus, amygdala, ventral tegmental area and nucleus accumbens.We evaluated a modest sample size of patients with concurrent pharmacological treatment using a subjective psychometric assessment.We highlight the importance of a dimensional and circuit-based approach to understanding target engagement and the mechanism of action of ECT, with the goal to define symptom- and circuit-specific response biomarkers for device neuromodulation therapies.

Deficits in cognitive control-that is, in the ability to withhold a default pre-potent response in favour of a more adaptive choice-are common in depression, anxiety, addiction and other mental disorders. Here we report proof-of-concept evidence that, in participants undergoing intracranial epilepsy monitoring, closed-loop direct stimulation of the internal capsule or striatum, especially the dorsal sites, enhances the participants' cognitive control during a conflict task. We also show that closed-loop stimulation upon the detection of lapses in cognitive control produced larger behavioural changes than open-loop stimulation, and that task performance for single trials can be directly decoded from the activity of a small number of electrodes via neural features that are compatible with existing closed-loop brain implants. Closed-loop enhancement of cognitive control might remediate underlying cognitive deficits and aid the treatment of severe mental disorders.

The aim of the current study was to compare the unified protocol for transdiagnostic treatment of emotional disorders (UP) with and without transcranial direct current stimulation (tDCS) for the treatment of emotion regulation and executive control dysfunction in individuals diagnosed with generalized anxiety disorder (GAD) and comorbid major depressive disorder (MDD). A total of 43 individuals with GAD and co-morbid MDD were randomly assigned to three groups including UP with tDCS (UP+tDCS; n = 15), UP alone (UP; n = 13) or wait-list control (n = 15). Difficulties in emotion regulation, reappraisal, suppression, inhibition and working memory were assessed at baseline, post-treatment and 3-month follow-up. Treatment with both UP+tDCS and UP alone resulted in significant improvements in difficulties in emotion regulation, cognitive reappraisal, and working memory, and significant reductions in suppression and inhibition relative to wait-list controls at post-treatment and 3-month follow-up. Relative to UP alone, UP+tDCS showed significantly greater improvements in difficulties in emotion regulation, cognitive reappraisal, inhibition, and working memory at post-treatment and 3-month follow-up. These results suggest combination of UP treatment with tDCS may be an efficacious intervention to improve emotion regulation and executive function in GAD with co-morbid MDD. Trial registration reference is IRCT20140929019334N1 (see https://irct.ir/trial/27988).

Background The ADHD Self Report Scale is a self-report measure that assesses attentional problems. We sought to validate the ASRS by establishing neural correlates using functional magnetic imaging in healthy controls and individuals with bipolar disorder (BD), who commonly exhibit attentional problems. Methods ASRS questionnaires and functional MRI data in conjunction with the Multi-source Interference Task (MSIT) were collected from 36 healthy control and 36 BD participants. We investigated task specific changes in the dorsal anterior cingulate cortex (dACC, Brodmann area 32) and their correlations with ASRS subscale scores, inattention and hyperactivity, in both cohorts. Results As hypothesized, the dACC showed significant increases in BOLD activation between the interference and noninterference conditions. For the ASRS scale as well as its Inattention and Hyperactivity subscales, there was a significant negative correlation with the dACC BOLD for the whole group. Conclusions The ASRS is sensitive to attentional difficulties in BD, suggesting that it is a valid tool for assessing attentional difficulties in patients with BD.

The aim of the current study was to compare the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) with and without transcranial direct current stimulation (tDCS) in individuals suffering from generalized anxiety disorder (GAD) and comorbid depression.A total of 43 individuals diagnosed with GAD and comorbid depression enrolled in a randomized controlled trial (IRCT20140929019334N1). Participants were randomly assigned to three groups including UP with tDCS (UP+tDCS; n = 15), UP alone (UP; n = 13) or wait-list control (n = 15). GAD and depression symptoms, worry severity, anxiety sensitivity, and intolerance of uncertainty were assessed at baseline, post-treatment and 3-month follow-up.Treatment with both UP+tDCS and UP alone resulted in significant lower ratings across all measures relative to wait-list controls at post-treatment and 3-month follow-up (all p-values0.001). UP+tDCS showed significantly greater reductions in anxiety (p = 0.001 post-treatment; p = 0.003 follow-up), worry (p = 0.001 post-treatment; p = 0.002 follow-up), and anxiety sensitivity (p = 0.003 post-treatment; p = 0.002 follow-up) relative to UP alone.The present study had some limitations. First, the sample size was low. Another limitation was the use of a short-term follow-up.These results suggest augmenting UP treatment with tDCS may be an efficacious strategy to improve treatment outcomes in GAD with comorbid depression. Trial registration reference is IRCT20140929019334N1 (see https://irct.ir/trial/27988).

Individuals with bipolar disorder are at greater risk for cardiovascular disease and are less likely to adhere to lifestyle interventions than the general population. To decrease cardiovascular risk and improve adherence to lifestyle interventions, we developed the Nutrition Exercise and Wellness Treatment (NEW Tx). NEW Tx is an 18 session, 20-week cognitive behavioral therapy (CBT)-based treatment comprising 3 modules: Nutrition, Exercise, and Wellness. To evaluate the feasibility and acceptability of this intervention as well as predictors of treatment satisfaction and expectations, 38 adult outpatients with bipolar disorder were randomized to either NEW Tx or a waitlist control condition. There was no statistically significant difference in drop-out rates between the groups (26.3% in NEW Tx, 31.6% in the control condition). In the NEW Tx condition, participants attended a mean of 66.7% of sessions and reported moderate to high satisfaction. There were no study-related adverse events. We also found that expectations, but not perceived credibility (or believability), of NEW Tx (as measured by the Credibility/ Expectancy Questionnaire) at baseline predicted treatment satisfaction (as measured by the Care Satisfaction Questionnaire) post-treatment. Manic symptoms at baseline predicted treatment satisfaction, and marital status predicted one’s expectations of lifestyle interventions. Data suggest that NEW Tx is a feasible and acceptable intervention for individuals with bipolar disorder and that further research is warranted to explore potential moderators of treatment expectations and credibility in this clinical population.

The Frontal Systems Behavior Scale (FrSBe) is a self-report measure that assesses difficulties with cognitive and emotional control such as apathetic behavior, lack of inhibitory control, and executive dysfunction. Previous neuroimaging studies highlight the involvement of the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex (DLPFC) in these processes. In this study, we investigated whether there was convergence across subjective and objective measures of apathy, disinhibition, and executive dysfunction. Specifically, we studied whether ACC, OFC, and DLPFC activation during a modified version of the Multi-Source Interference Task (MSIT), is associated with FrSBe apathy, disinhibition, and executive dysfunction scores, in healthy controls (HC) and individuals with Bipolar Disorder (BD), who commonly exhibit difficulties in these domains. Individuals with BD (n = 31) and HCs (n = 31) with no current or past psychiatric illness completed the FrSBe and the MSIT during fMRI scanning. We investigated task-specific changes in the ACC, DLPFC, and OFC and their correlations with FrSBe apathy, disinhibition, and executive dysfunction subscale scores, respectively. Individuals with BD and the HC group demonstrated greater ACC, DLPFC, and OFC activation during MSIT interference conditions compared with non-interference conditions. Furthermore, there was a significant negative correlation between OFC activation and disinhibition scores, which remained significant after accounting for medication load. Together, these results demonstrate the FrSBe disinhibition subscale, in particular, can be a self-report measure that converges with behavioral and neural markers of disinhibition in BD.

Unipolar and bipolar depression are virtually indistinguishable at the behavioral level, yet likely show meaningful differences in underlying pathophysiology. Resting-state magnetic resonance imaging (rsfMRI) has provided a methodological window into the pathophysiology of mood disorders at the level of neurocircuitry, with greater potential for methodological standardization and generalizability than traditional task-based approaches. In this chapter, we review the existing rsfMRI literature on unipolar and bipolar depression, in an attempt to synthesize findings and probe both the overlap and divergence in neurocircuit function underlying these disorders. Existing rsfMRI studies of unipolar and bipolar depression converge upon disrupted functional connectivity within neural networks supporting self-referential (default mode network), affective and reward (salience network), and executive control (frontoparietal control network) functions. Unipolar depression is distinguished from bipolar depression by increased default mode and decreased salience network within-network functional connectivity. In contrast, bipolar depression is distinguished from unipolar depression by more diffuse disruptions in cortico-striatal-limbic-subcortical and somatosensory functional connectivity. Challenges to the interpretation of rsfMRI and implications for future intervention development are discussed.

Bipolar Disorder (BD) involves altered neural affective processing, but studies comparing BD patients to controls have yielded inconsistent results. This might relate to substantial variability in the nature and severity of mood symptoms among individuals with BD. Hence, we dimensionally examined the relationship between depressive and manic symptom severity and neural responses to positive and negative affective stimuli. 39 Participants with BD completed measures of depression and mania severity prior to completing a cognitive-affective processing task during fMRI. A multiple regression model was run in SPM to identify brain regions correlated with depressive and manic symptoms during positive-neutral and negative-neutral contrasts. A-priori anatomical ROIs were defined bilaterally in frontal, parietal and limbic regions. Results showed that depression severity was associated with increased activation in frontal, parietal, and limbic ROIs, regardless of valence. Mania severity was correlated with both increased and decreased activation, particularly within frontal subdivisions and during the processing of positively valenced images. In conclusion, dimensional modeling of symptom severity captures variance in neural responses to affect, which may have been previously undetected due to heterogeneity when examined at the group level. Future fMRI studies comparing BD patients and controls should account for symptom variability in BD.

Cognitive control is the ability to withhold a default, prepotent response in favor of a more adaptive choice. Control deficits are common across mental disorders, including depression, anxiety, and addiction. Thus, a method for improving cognitive control could be broadly useful in disorders with few effective treatments. Here, we demonstrate closed-loop enhancement of one aspect of cognitive control by direct brain stimulation in humans. We stimulated internal capsule/striatum in participants undergoing intracranial epilepsy monitoring as they performed a cognitive control/conflict task. Stimulation enhanced performance, with the strongest effects from dorsal capsule/striatum stimulation. We then developed a framework to detect control lapses and stimulate in response. This closed-loop approach produced larger behavioral changes than open-loop stimulation, with a slight improvement in performance change per unit of energy delivered. Finally, we decoded task performance directly from activity on a small number of electrodes, using features compatible with existing closed-loop brain implants. Our findings are proof of concept for a new approach to treating severe mental disorders, based on directly remediating underlying cognitive deficits.

The ability to regulate emotions in the service of meeting ongoing goals and task demands is a key aspect of adaptive human behavior in our volatile social world. Consequently, difficulties in processing and responding to emotional stimuli underlie many psychiatric diseases ranging from depression to anxiety, the common thread being effects on behavior. Behavior, which is made up of shifting, difficult to measure hidden states such as attention and emotion reactivity, is a product of integrating external input and latent mental processes. Directly measuring, and differentiating, separable hidden cognitive, emotional, and attentional states contributing to emotion conflict resolution, however, is challenging, particularly when only using task-relevant behavioral measures such as reaction time. State-space representations are a powerful method for investigating hidden states underlying complex systems. Using state-space modeling of behavior, we identified relevant hidden cognitive states and predicted behavior in a standardized emotion regulation task. After identifying and validating models which best fit the behavior and narrowing our focus to one model, we used targeted intracranial stimulation of the emotion regulation-relevant neurocircuitry, including prefrontal structures and the amygdala, to causally modulate separable states. Finally, we focused on this one validated state-space model to perform real-time, bidirectional closed-loop adaptive stimulation in a subset of participants. These approaches enable an improved understanding of how to sample and understand emotional processing in a way which could be leveraged in neuromodulatory therapy for disorders of emotional regulation.

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis) and bipolar disorder have been associated with dysregulated mitochondrial and brain energy metabolism, PGC-1 alpha may represent a potential drug target for these conditions. The purpose of this article is to review the physiology of PGC-1 alpha, PPARs, and the role of PPAR agonists to target PGC-1 alpha to treat neurodegenerative diseases and bipolar disorder. We also review clinical trials of repurposed antidiabetic thiazolidines and anti-triglyceride fibrates (PPAR agonists) for neurodegenerative diseases and bipolar disorder. PGC-1 alpha and PPARs are innovative potential targets for bipolar disorder and warrant future clinical trials.

Recent emotion dysregulationmodels of generalized anxiety disorder (GAD) propose chronic worry in GAD functions as a maladaptive attempt to regulate anxiety related to uncertain or unpredictable outcomes. Emotion acceptance is an adaptive emotion regulation strategy increasingly incorporated into newer cognitive behavioral therapy (CBT) approaches to GAD to counter chronic worry. The current study explores themechanisms of emotion acceptance as an alternate emotion regulation strategy to worry or emotion suppression using functionalmagnetic resonance imaging. Twenty-one female participants diagnosed with GAD followed counterbalanced instructions to regulate responses to personally relevant worry statements by engaging in either emotion acceptance, worry or emotion suppression. Emotion acceptance resulted in lower ratings of distress than worry and was associated with increased dorsal anterior cingulate cortex (dACC) activation and increased ventrolateral prefrontal cortex (VLPFC)-amygdala functional connectivity. In contrast, worry showed significantly greater distress ratings than acceptance or suppression and was associated with increased precuneus, VLPFC, amygdala and hippocampal activation. Suppression did not significantly differ fromacceptance in distress ratings or amygdala recruitment, but resulted in significantly greater insula and VLPFC activation and decreased VLPFC-amygdala functional connectivity. Emotion acceptance closely aligned with activation and connectivity patterns reported in studies of contextual extinction learning and mindful awareness., National Institute of Mental Health (U.S.) (Grant F31 MH084422)

Mental disorders are a leading cause of disability, morbidity, and mortality among civilian and military populations. Most available treatments have limited efficacy, particularly in disorders where symptoms vary over relatively short time scales. Targeted modulation of neural circuits, particularly through open-loop deep brain stimulation (DBS), showed initial promise but has failed in blinded clinical trials. We propose a new approach, based on targeting neural circuits linked to functional domains that cut across diagnoses. Through that framework, which includes measurement of patients using six psychophysical tasks, we seek to develop a closed-loop DBS system that corrects dysfunctional activity in brain circuits underlying those domains. We present convergent preliminary evidence from functional neuroimaging, invasive human electrophysiology, and human brain stimulation experiments suggesting that this approach is feasible. Using the Emotional Conflict Resolution (ECR) task as an example, we show that emotion-related networks can be identified and modulated in individual patients. Invasive and non-invasive methodologies both identify a network between prefrontal cortex, cingulate cortex, insula, and amygdala. Further, stimulation in cingulate and amygdala changes patients' performance in ways that are linked to the task's emotional content. We present preliminary statistical models that predict this change and allow us to track it at a single-trial level. As these diagnostic and modeling strategies are refined and embodied in an implantable device, they offer the prospect of a new approach to psychiatric treatment and its accompanying neuroscience.

Approach-avoidance conflict arises when the drives to pursue reward and avoid harm are incompatible. Previous neuroimaging studies of approach-avoidance conflict have shown large variability in reported neuroanatomical correlates. These prior studies have generally neglected to account for potential sources of variability, such as individual differences in choice preferences and modeling of hemodynamic response during conflict. In the present study, we controlled for these limitations using a hierarchical Bayesian model (HBM). This enabled us to measure participant-specific per-trial estimates of conflict during an approach-avoidance task. We also employed a variable epoch method to identify brain structures specifically sensitive to conflict. In a sample of 28 human participants, we found that only a limited set of brain structures [inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex (dlPFC), and right pre-supplementary motor area (pre-SMA)] are specifically correlated with approach-avoidance conflict. These findings suggest that controlling for previous sources of variability increases the specificity of the neuroanatomical correlates of approach-avoidance conflict.

Background Individuals with bipolar disorder (BD) are more likely than the general population to develop risk factors associated with cardiovascular disease, one of the leading causes of morbidity and mortality in this clinical population. To address this disproportionate medical burden, we developed Nutrition Exercise and Wellness Treatment (NEW Tx), a lifestyle intervention for individuals with BD. Methods In this study, participants were randomized to NEW Tx (n = 19) or a treatment as usual waitlist (n = 19). We examine the intervention's efficacy to improve the physical and psychological outcomes of individuals with BD. Assessors were blind to participant condition throughout study duration. Results The NEW Tx group reported increased weekly exercise duration and overall functioning, and decreased depression and illness severity over the study duration. However, only improvements in functioning were significantly greater in the NEW Tx group than in the control group. There were no group differences in weight loss or mood symptoms over the study duration. Limitations Limitations to this study include lack of objective measurement of exercise and a small and relatively homogeneous sample. Conclusions These data suggest that a manualized lifestyle intervention for BD may not be ideal to improve lifestyle changes in this clinical population. Further research is needed to pilot personalized approaches to creating a healthy lifestyle in BD.

Background Anxiety in bipolar disorder (BD) exacerbates emotion dysregulation and reduces treatment response. We recently conducted a pilot trial of transdiagnostic CBT to target anxiety and emotion dysregulation in BD adjunctive to pharmacotherapy. Reductions in depression and anxiety symptoms were significantly predicted by baseline levels of neuroticism and perceived affective control, as well as changes over time in emotion regulation skills. The present study investigates mechanism of treatment response by examining the relationship between baseline emotion regulation-related neural circuitry and trial outcomes. Methods Nineteen patients completed baseline resting state fMRI scans prior to treatment randomization. Functional connectivity between the anterior insula (AI) and regions in the salience network (SN), default mode network (DMN), and executive control network (ECN) were examined as predictors of baseline and treatment-related changes in emotion regulation. Results Greater improvements in emotion regulation were predicted by weaker right dorsal AI – right ventrolateral prefrontal cortex (VLPFC; SN) and stronger bilateral dorsal AI – bilateral amygdala functional connectivity. Baseline neuroticism was negatively correlated with right dorsal AI- inferior parietal lobule (ECN) functional connectivity, and baseline deficits in perceived affective control were positively associated with ventral AI – bilateral dACC (SN) connectivity. Limitations Small sample limits interpretability of treatment-specific effects. Conclusion Baseline functional connectivity of emotion-regulation related neural circuitry significantly predicted change in emotion regulation-related dimensions associated with anxiety and depression symptom reduction. Future studies are needed to determine if employing methods such as neuromodulation to rehabilitate relevant neural circuitry may improve ultimate treatment outcomes of transdiagnostic CBT for BD and anxiety.

Background Patients with bipolar depression are characterized by dysregulation across the full spectrum of mood, differentiating them from patients with unipolar depression. The ability to switch neural resources among the default mode network, salience network, and executive control network (ECN) has been proposed as a key mechanism for adaptive mood regulation. The anterior insula is implicated in the modulation of functional network switching. Differential connectivity between anterior insula and functional networks may provide insights into pathophysiological differences between bipolar and unipolar mood disorders, with implications for diagnosis and treatment. Methods Resting-state functional magnetic resonance imaging data were collected from 98 subjects (35 unipolar, 24 bipolar, and 39 healthy control subjects). Pearson correlations were computed between bilateral insula seed regions and a priori defined target regions from the default mode network, salience network, and ECN. After r-to-z transformation, a one-way multivariate analysis of covariance was conducted to identify significant differences in connectivity between groups. Post hoc pairwise comparisons were conducted and Bonferroni corrections were applied. Receiver-operating characteristics were computed to assess diagnostic sensitivity. Results Patients with bipolar depression evidenced significantly altered right anterior insula functional connectivity with the inferior parietal lobule of the ECN relative to patients with unipolar depression and control subjects. Right anterior insula–inferior parietal lobule connectivity significantly discriminated patients with bipolar depression. Conclusions Impaired functional connectivity between the anterior insula and the inferior parietal lobule of the ECN distinguishes patients with bipolar depression from those with unipolar depression and healthy control subjects. This finding highlights a pathophysiological mechanism with potential as a therapeutic target and a clinical biomarker for bipolar disorder, exhibiting reasonable sensitivity and specificity.

Objective This pilot randomized controlled trial compared Cognitive Behavior Therapy (CBT) and Supportive Psychotherapy (SP) for the treatment of depression in bipolar I disorder. We also examined whether exploratory verbal memory, executive functioning, and neural correlates of verbal memory during functional magnetic resonance imaging (fMRI) predicted change in depression severity. Methods Thirty-two adults (ages 18–65) with DSM-IV bipolar I disorder meeting current criteria for a major depressive episode were randomized to 18 weeks of CBT or SP. Symptom severity was assessed before, at the mid-point, and after the 18-week intervention. All participants completed a brief pre-treatment neuropsychological testing battery (including the California Verbal Learning Test-2nd Edition, Delis Kaplan Executive Functioning System [DKEFS] Trail-making Test, and DKEFS Sorting Test), and a sub-set of 17 participants provided usable fMRI data while completing a verbal learning paradigm that consisted of encoding word lists. Results CBT and SP yielded comparable improvement in depressive symptoms from pre- to post-treatment. Better retention of learned information (CVLT-II long delay free recall vs. Trial 5) and recognition (CVLT-II hits) were associated with greater improvement in depression in both treatments. Increased activation in the left dorsolateral prefrontal cortex and right hippocampus during encoding was also related to depressive symptom improvement. Limitations Sample size precluded tests of clinical factors that may interact with cognitive/neural function to predict treatment outcome. Conclusion Neuropsychological assessment and fMRI offer additive information regarding who is most likely to benefit from psychotherapy for bipolar depression.

OBJECTIVES: Bipolar disorders (BD) are characterized by emotion and cognitive dysregulation. Mapping deficits in the neurocircuitry of cognitive-affective regulation allows for potential identification of intervention targets. The current study used functional MRI data in BD patients and healthy controls during performance on a task requiring cognitive and inhibitory control superimposed on affective images, assessing cognitive and affective interference. METHODS: Functional MRI data were collected from 39 BD patients and 36 healthy controls during performance on the Multi-Source Interference Task overlaid on images from the International Affective Picture System (MSIT-IAPS). Analyses examined patterns of activation in a priori regions implicated in cognitive and emotional processing. Functional connectivity to the anterior insula during task performance was also examined, given this region’s role in emotion-cognition integration. RESULTS: BD patients showed significantly less activation during cognitive interference trials in inferior parietal lobule, dorsomedial prefrontal cortex, anterior insula, mid-cingulate, and ventrolateral prefrontal cortex regardless of affective valence. BD patients showed deviations in functional connectivity with anterior insula in regions of the default mode and frontoparietal control networks during negatively valenced cognitive interference trials. CONCLUSIONS: Our findings show disruptions in cognitive regulation and inhibitory control in BD patients in the presence of irrelevant affective distractors. Results of this study suggest one pathway to dysregulation in BD is through inefficient integration of affective and cognitive information, and highlight the importance of developing interventions that target emotion-cognition integration in BD.

Chapter 8 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Workbook looks at one part of our emotional experiences—our thoughts—and describes how thoughts are very important for influencing how we feel. The chapter describes our tendency to get stuck in automatic patterns of thinking, which we refer to as thinking traps. This treatment describes two specific types of thinking traps: jumping to conclusions and thinking the worst. Next, readers are encouraged to identify their own patterns of negative thinking to generate alternative interpretations. The overall goal is to be more flexible in our thinking, referred to as cognitive flexibility.

Chapter 9 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Workbook looks at another part of our emotional experiences—emotional behaviors, which refer to the things we do to manage our emotions. This chapter presents skills to help us identify and evaluate our emotional behaviors by examining both the short term and long term consequences of these actions. In general, unhelpful emotional behaviors provide short term relief from strong emotions but set us up to experience even more strong emotions in the future. Lastly, we learn to counter unhelpful emotional behaviors by replacing current emotional behaviors with new, alternative behaviors, a skill called choosing an Alternative Action.

Chapter 5 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide is designed to provide a review of the patient’s presenting problems and diagnoses within the context of the emotional disorder framework. This is an opportunity for the therapist to start identifying how the patient’s experience fits into a transdiagnostic model emphasizing frequent strong emotions and aversive, avoidant responses to these emotions. This first session also emphasizes the importance of cultural factors and then provides patients with an introduction to the treatment protocol.

Chapter 1 of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide introduces the treatment program, which is applicable to all anxiety and unipolar depressive disorders, and potentially other disorders with strong emotional components (e.g., eating disorders, borderline personality disorder). This introductory chapter lays out the advantages of a unified, transdiagnostic approach as well as the efficacy of the Unified Protocol (UP). The chapter concludes with an explanation of the purpose of the therapist guide, which gives mental health providers guidance on administration of the UP.

Chapter 4 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Workbook focuses on identifying ways that your emotional responding is interfering with your lives—the top problems you would like to change and how determine the specific steps needed to address these problems. The importance of maintaining motivation for making these difficult changes is also discussed. The topics covered in this chapter form the necessary foundation for building a healthier relationship with our emotions. The rest of the skills in this book build upon this groundwork. This chapter also explores the costs and benefits of changing and remaining the same.

Chapter 7 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide provides psychoeducation on the functional, adaptive nature of emotions and assists patients in developing greater awareness of patterns of emotional responding, including potential maintaining factors (e.g., common triggers, environmental contingencies, and/or the maintaining role of avoidance). Patients also learn how to monitor and track their emotions by focusing on three core components of their emotional experiences (thoughts, physical feelings, and behaviors).

The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Workbook was developed to help people who are struggling with intense emotions like anxiety, sadness, anger, and guilt. A person may have an emotional disorder when his or her emotions are so overwhelming that they get in the way of moving forward in life. Although emotions affect our lives in different ways, there are three features that often occur across emotional disorders. These are (a) frequent, strong emotions; (b) negative reactions to emotions; and (c) avoidance of emotions. The goal of this workbook is to change the way that people with emotional disorders respond to their emotions when they occur. This treatment program is applicable to all anxiety and unipolar depressive disorders and potentially other disorders with strong emotional components. The strategies included in this treatment are largely based on common principles found in existing empirically supported psychological treatments.

Chapter 3 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide covers assessment, monitoring, and medication. The chapter also clarifies who will benefit from the UP program as well as the benefits for patients of using the corresponding workbook. This chapter addresses what to do if other emotional problems are present and who should administer the program.

Chapter 11 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide focuses on interoceptive exposure, or exposure to physical sensations that are associated with (and can sometimes trigger) intense emotions. The exercises described in the UP workbook are designed to assist patients in gaining further awareness of physical sensations that are part of an emotional reaction. Further, these exercises, and continued exposures focused on physical sensations, are expected to help patients learn to tolerate and think differently about the sensations and provide an opportunity to break the conditioned association between the sensations and strong emotions such as fear, anxiety, and sadness.

Chapter 9 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide focuses on one very important component of emotional experiences: thoughts. Specifically, therapists will teach their patients to develop a greater awareness of how patient thoughts (or interpretations) influence their emotions, to learn to identify their negative thinking patterns, and to increase flexibility in interpreting different situations. The concepts introduced in this chapter are aimed to facilitate patients’ ability to approach emotion-provoking situations and respond to their emotions in more helpful, adaptive ways.

Chapter 13 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide provides information for the therapist and does not correspond to a particular therapy session. There is tremendous variability in the extent to which individuals use medication, psychological treatment, or some combination of the two. If a particular patient is using medication, discontinuation may be addressed toward the end of therapy when patients are beginning to feel better and more confident in their ability to manage their symptoms without medication. This chapter addresses some reasons for medication use and how medication use might affect treatment. It also provides information on how medications can be discontinued.

Chapter 2 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide notes that the Unified Protocol (UP) is based on traditional cognitive-behavioral principles, but the particular emphasis on the way individuals experience and respond to their emotions is unique in that it brings emotional processes to the forefront, making them available to fundamental psychological mechanisms of change. Core skills of the UP are introduced. These include mindful emotion awareness, which involves the practice of nonjudgmental, present-focused attention toward emotional experiences; challenging automatic thoughts related to external threats and internal threats and increasing cognitive flexibility; identifying and modifying problematic action tendencies, or emotional behaviors; increasing awareness and tolerance of physical sensations through interoceptive exposures; and engagement in emotion exercises. The chapter concludes with a description of the treatment modules.

Chapter 12 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Workbook describes medications that are commonly prescribed for emotional disorders. These include anti-anxiety medications such as benzodiazepines and beta blockers, as well as antidepressant medications like selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. In addition, individuals with emotional disorders are sometimes prescribed mood stabilizers or antipsychotic medications. The chapter answers frequently asked questions about medications. It also provides recommendations for how to discontinue medications under the supervision of the prescribing physician. This treatment program can be completed in combination with the use of medication and considerations for this practice are described in this chapter.

Chapter 13 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Workbook reviews the treatment program. (1) All emotions, even the ones that feel negative or uncomfortable, provide important information that can motivate us to take action in helpful ways. (2) Staying present in the moment and taking a nonjudgmental view of emotions can help to prevent emotions from increasing in intensity. The way we think about a situation influences how we feel, and how we feel affects the way we interpret a situation. (3) Although avoiding uncomfortable emotional experiences can work well in the short-term, it isn’t an effective long-term coping strategy. The chapter helps us to evaluate our progress and revisit our treatment goals. The most effective way to maintain progress and to keep improving is to continue to practice the skills learned in this program, and therefore a practice plan is developed in this last chapter.

Chapter 8 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide introduces patients to cultivating a nonjudgmental, present-focused stance toward their emotional experiences. The previous module asked patients to monitor to how their emotions unfold over time. This module builds on that work by encouraging patients to incorporate mindful awareness that moves beyond simply paying attention to these experiences. The principles of mindfulness are very consistent with the overall goal of the UP—to develop a more open, approach-oriented relationship with emotions.

Chapter 10 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Workbook looks at the third part of an emotional experience—the physical sensations associated with our emotions. Physical sensations refer to any physical symptoms that we might experience during strong emotions (e.g., racing heart, sweating, or nausea). We learn to identify these physical sensations and how they impact our experience of emotions. We then learn to confront uncomfortable physical sensations through physical exercises designed to bring on the sensations that come up when we have strong emotions. We do this because facing physical sensations over and over makes them easier to tolerate.

Chapter 12 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide focuses on Emotion Exposures. These are exercises designed specifically to provoke strong emotional responses so that patients can put into practice the skills they have developed thus far in therapy. Following a brief introduction to the concept of Emotion Exposures and the rationale for engaging in these exercises, therapists assist patients to gradually confront internal and external stimuli that produce intense emotional reactions while helping them modify their responses to those emotions. Therapists will help patients incorporate the skills learned in therapy (present-focused awareness, nonjudgment, cognitive reappraisal) into their exposure practice and address any emotion avoidance (or other behaviors) that may impede treatment progress.

Chapter 15 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide looks at providing the UP treatment in a group format. Benefits of group therapy (such as efficiency, patients supporting one another) are discussed. Although the authors always intended for the UP to be a treatment that could be used in either an individual or group format, most of the studies to date have looked at how the UP works in an individual format. Therefore, the authors are still learning the best way to teach the strategies in a group format. Some recommendations for how to adapt the UP for a group format are provided. These look at structure, treatment rationale, flexible application of the UP model, and conducting emotion exposures in a group format.

Chapter 14 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide evaluates the patient’s progress and to plan for the future. Therapists will also reinforce the skills learned in treatment, review key treatment concepts, and help patients develop strategies for preventing “relapse.” Additionally, this chapter is used to address symptom recurrence and how patients can maintain treatment gains in the long term.

Chapter 6 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Therapist Guide was designed to help patients clarify the top problem areas in which emotions interfere with their ability to function and to begin to identify concrete steps to take in order to achieve the desired change. This module provides two exercises for enhancing the motivation necessary in initiating this type of treatment program and can be reviewed as needed throughout the course of treatment. The purpose of this module is to maximize the patient’s readiness for change and increase motivation to engage in treatment. Troubleshooting problems with filling out the forms is also covered.

Chapter 1 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Workbook describes the types of problems the Unified Protocol (UP) program was designed to address. The chapter begins by defining emotional disorders, which are characterized by the frequent experience of strong emotions, negative reactions to these emotional experiences, and efforts to escape or avoid them. Next, the types of disorders that that fit within the larger class of emotional disorders, and are addressed by the is treatment, are described. Finally, this chapter helps readers determine whether this treatment is a good fit for the types of problems they are experiencing.

Chapter 7 of Unified Protocol for Transdiagnostic Treatment of Emotional Disorders: Workbook presents the benefits of applying mindful awareness, a nonjudgmental present-focused stance, to emotional experiences. Mindful awareness is first practiced through a formal meditation exercise that introduces readers to applying this quality of attention to their emotions. Next, readers are encouraged to continue practicing mindful emotion awareness though the use of a Mindful Mood Induction exercise. Finally, the chapter continues by focusing on the Anchoring in the Present skill, which allows us to apply the concept of mindful emotion awareness to emotional experiences as they are coming up in daily life.