Brain activity during reappraisal and associations with psychotherapy response in social anxiety and major depression: a randomized trial.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective treatment for patients with social anxiety disorder (SAD) or major depressive disorder (MDD), yet there is variability in clinical improvement. Though prior research suggests pre-treatment engagement of brain regions supporting cognitive reappraisal (e.g. dorsolateral prefrontal cortex [dlPFC]) foretells CBT response in SAD, it remains unknown if this extends to MDD or is specific to CBT. The current study examined associations between pre-treatment neural activity during reappraisal and clinical improvement in patients with SAD or MDD following a trial of CBT or supportive therapy (ST), a common-factors comparator arm. METHODS: Participants were 75 treatment-seeking patients with SAD (n = 34) or MDD (n = 41) randomized to CBT (n = 40) or ST (n = 35). Before randomization, patients completed a cognitive reappraisal task during functional magnetic resonance imaging. Additionally, patients completed clinician-administered symptom measures and a self-report cognitive reappraisal measure before treatment and every 2 weeks throughout treatment. RESULTS: Results indicated that pre-treatment neural activity during reappraisal differentially predicted CBT and ST response. Specifically, greater trajectories of symptom improvement throughout treatment were associated with less ventrolateral prefrontal cortex (vlPFC) activity for CBT patients, but more vlPFC activity for ST patients. Also, less baseline dlPFC activity corresponded with greater trajectories of self-reported reappraisal improvement, regardless of treatment arm. CONCLUSIONS: If replicated, findings suggest individual differences in brain response during reappraisal may be transdiagnostically associated with treatment-dependent improvement in symptom severity, but improvement in subjective reappraisal following psychotherapy, more broadly.

Crime Risk and Depression Differentially Relate to Aspects of Sleep in Patients with Major Depression or Social Anxiety.

Individuals with internalizing conditions such as depression or anxiety are at risk of sleep difficulties. Social-ecological models of sleep health propose factors at the individual (e.g., mental health) and neighborhood (e.g., crime risk) levels that contribute to sleep difficulties. However, these relationships have been under-researched in terms of internalizing conditions. Therefore, the current study comprised participants diagnosed with major depression (n = 24) or social anxiety (n = 35). Sleep measures included actigraphic variables (i.e., total sleep time, waking after sleep onset, sleep onset latency) and subjective sleep quality. Geocoding was used to assess nationally-normed crime risk exposure at the person level (e.g., murder, assault) and property level (e.g., robbery, burglary). Analyses consisted of independent t-tests to evaluate potential differences between diagnostic groups. To examine relationships, multiple regressions were used with internalizing symptoms, crime risk, and age as independent variables and sleep measures as the dependent variable. The t-test results revealed that groups differed in symptoms and age but not sleep or neighborhood crime. Regression results revealed crime risk positively corresponded with sleep onset latency but no other sleep measures. Also, only depression positively corresponded with total sleep time. Preliminary findings suggest exposure to crime and depression relate differentially to facets of sleep in individuals with internalizing conditions.

Default Mode Network Hypoalignment of Function to Structure Correlates With Depression and Rumination.

BACKGROUND: Recent studies have begun to examine how signals in the brain correspond to the underlying white matter structure using tools from the field of graph signal processing to quantify brain function alignment to brain network topology. Here, we applied this framework for the first time toward a transdiagnostic cohort of individuals with internalizing psychopathologies, including mood and anxiety disorders, to uncover how such alignment within the default mode network (DMN) is related to depression and rumination symptoms. METHODS: Both diffusion-weighted and resting-state functional magnetic resonance imaging were obtained from participants at baseline (n = 60 patients, n = 19 healthy control participants). Patients were randomized to 12 weeks of treatment with either a selective serotonin reuptake inhibitor or cognitive behavioral therapy, and symptom scales were readministered posttreatment (n = 46 patients at follow-up). Using graph signal processing methodology, we quantified the alignment of functional signals to their underlying white matter structural networks. RESULTS: We found that signal alignment within the posterior DMN was decreased in patients with internalizing psychopathologies compared with healthy control participants and was inversely (negatively) correlated with baseline depression and rumination scales. Signal alignment within the posterior DMN was also correlated with the ratio of total within-DMN to extra-DMN functional connectivity for these regions. CONCLUSIONS: These findings are consistent with previous literature regarding pathological promiscuity of posterior DMN connectivity and provide the first graph signal processing-based analyses in a transdiagnostic cohort of patients with internalizing psychopathologies.

Network Analysis of Behavioral Activation/Inhibition Systems and Brain Volume in Individuals With and Without Major Depressive Disorder or Social Anxiety Disorder.

BACKGROUND: Social anxiety disorder (SAD) and major depressive disorder (MDD) are characterized by behavioral abnormalities in motivational systems, namely the behavioral inhibition system (BIS) and behavioral activation system (BAS). Limited studies indicate brain volume in regions that support emotion, learning/memory, reward, and cognitive functions relate to BIS/BAS. To increase understanding of BIS/BAS, the current study used a network approach. METHODS: Patients with SAD (n = 59), patients with MDD (n = 64), and healthy control participants (n = 36) completed a BIS/BAS questionnaire and structural magnetic resonance imaging scans; volumetric regions of interest comprised cortical and limbic structures based on previous BIS/BAS studies. A Bayesian Gaussian graphical model was used for each diagnostic group, and groups were compared. Among network metrics, bridge centrality was of primary interest. Analysis of variance evaluated BIS/BAS behaviors between groups. RESULTS: Bridge centrality showed hippocampus positively related to BAS, but not to BIS, in the MDD group; no findings were observed in the SAD or control groups. Yet, network density (i.e., overall strength of relationships between variables) and degree centrality (i.e., overall relationship between one variable to all other variables) showed that cortical (e.g., precuneus, medial orbitofrontal) and subcortical (e.g., amygdala, hippocampus) regions differed between diagnostic groups. Analysis of variance results showed BAS was lower in the MDD/SAD groups compared with the control group, while BIS was higher in the SAD group relative to the MDD group, which in turn was higher than the control group. CONCLUSIONS: Preliminary findings indicate that network-level aberrations may underlie motivational abnormalities in MDD and SAD. Evidence of BIS/BAS differences builds on previous work that points to shared and distinct motivational differences in internalizing psychopathologies.

Objective and Subjective Sleep Measures Are Related to Suicidal Ideation and Are Transdiagnostic Features of Major Depressive Disorder and Social Anxiety Disorder.

Suicide is a major public health problem and previous studies in major depression and anxiety show problematic sleep is a risk factor for suicidal ideation (SI). However, less is known about sleep and SI in social anxiety disorder (SAD), despite the pervasiveness of SAD. Therefore, the current study comprised participants with major depressive disorder (MDD) (without comorbid SAD) (n = 26) and participants with SAD (without comorbid MDD) (n = 41). Wrist actigraphy was used to estimate sleep duration, wake after sleep onset, and sleep efficiency; sleep quality was evaluated with self-report. Self-report was also used to examine SI. These measures were submitted to independent t-tests and multiple regression analysis. t-test results revealed sleep and SI did not differ between MDD and SAD groups. Multiple regression results showed shorter sleep duration and worse sleep quality related to greater SI when taking symptom severity and age into account. Post-hoc partial correlational analysis showed these sleep-SI relationships remained significant after controlling for symptom severity and age. Preliminary findings indicate sleep and SI may be transdiagnostic features of MDD and SAD. Evidence of distinct sleep-SI relationships are consistent with previous reports showing that sleep difficulties contribute to SI. Altogether, improving sleep duration and sleep quality may reduce the risk of SI.

Differential effects of transcranial current type on heart rate variability during emotion regulation in internalizing psychopathologies.

BACKGROUND: Internalizing psychopathologies (IPs) are characterized by disruptions in emotion regulation (ER). A potential target for ER modulation in individuals with IPs is the theta band. We hypothesized that offset theta-tACS (transcranial alternating current stimulation) would result in more enhanced ER, indexed by greater increase in heart rate variability (HRV), than transcranial direct current stimulation (tDCS) in participants with IPs. METHODS: This pilot study utilized a double-blind, pseudo-counterbalanced design. Participants with internalizing psychopathologies (anxiety and depression) were randomly assigned to receive either offset theta-tACS (n = 14) or tDCS (n = 15) and underwent four sessions of stimulation (two sham). In both arms, there were alternating iterations of an emotion regulation task (ERT) during or immediately after stimulation and rest. Heart rate data were collected during each ERT and rest iteration, and analyses were completed using high-frequency (HF) and root mean square of successive differences (RMSSD) HRV metrics. RESULTS: tACS participants consistently displayed increases in both HRV metrics from Time 1 to Time 4. Participants receiving tDCS displayed few significant changes in HF-HRV and no significant changes in RMSSD-HRV. LIMITATIONS: Due to the small sample size, analyses were limited. Additionally, the lack of a baseline ERT makes it difficult to determine overall ER improvement. CONCLUSIONS: tACS appears to increase ER capacity as reflected in increased HRV in individuals with internalizing psychopathologies, particularly after two sessions of stimulation. This study adds validity to the use of tACS as a neuromodulatory technique in cognitive and clinical research. Additional research is required to better understand potential carry-over effects of multiple sessions of stimulation.

Neural responsiveness to reward and suicidal ideation in social anxiety and major depression before and after psychotherapy.

Suicidality is prevalent in Social Anxiety Disorder (SAD) and Major Depressive Disorder (MDD). Limited data indicate the reward positivity (RewP), a neurophysiological index of reward responsivity, and subjective capacity for pleasure may serve as brain and behavioral assays for suicide risk though this has yet to be examined in SAD or MDD in the context of psychotherapy. Therefore, the current study tested whether suicidal ideation (SI) relates to RewP and subjective capacity for anticipatory and consummatory pleasure at baseline and whether Cognitive Behavioral Therapy (CBT) impacts these measures. Participants with SAD (n = 55) or MDD (n = 54) completed a monetary reward task (gains vs. losses) during electroencephalogram (EEG) before being randomized to CBT or supportive therapy (ST), a comparator common factors arm. EEG and SI data were collected at baseline, mid-treatment, and post-treatment; capacity for pleasure was collected at baseline and post-treatment. Baseline results showed participants with SAD or MDD were comparable in SI, RewP, and capacity for pleasure. When controlling for symptom severity, SI negatively corresponded with RewP following gains and SI positively corresponded with RewP following losses at baseline. Yet, SI did not relate to subjective capacity for pleasure. Evidence of a distinct SI-RewP association suggests RewP may serve as a transdiagnositic brain-based marker of SI. Treatment outcome revealed that among participants with SI at baseline, SI significantly decreased regardless of treatment arm; also, consummatory, but not anticipatory, pleasure increased across participants regardless of treatment arm. RewP was stable following treatment, which has been reported in other clinical trial studies.

Actigraphic Wake after Sleep Onset and Symptom Severity Correspond with Rumination in Trauma-Exposed Individuals.

Rumination and worry are forms of repetitive negative thinking (RNT) commonly associated with internalizing psychopathologies, although less is known about RNT in trauma-exposed individuals with internalizing psychopathologies. Separate lines of research show RNT also plays a role in problematic sleep, which is frequently experienced after trauma exposure. To address gaps in the literature, the current study examines the impact of sleep and symptoms on RNT in trauma-exposed participants. A transdiagnostic sample of 46 unmedicated treatment-seeking trauma-exposed participants completed standard measures of rumination and worry, as well as clinical measures that assessed posttraumatic stress, depression, and anxiety severity. Actigraphic sleep variables were sleep duration, wake after sleep onset (WASO), and sleep efficiency. Sleep and clinical measures were submitted to multiple regression analyses with rumination and worry as dependent variables. The regression results showed that rumination was significantly explained by WASO and posttraumatic stress symptom (PTSS) severity, and the omnibus test was significant. Depression, anxiety, and other estimates of sleep were not significant. No significant results emerged for worry. Preliminary findings suggest that PTSS and WASO, an index of fragmented sleep, may contribute to rumination, but not worry, in trauma-exposed individuals. Longitudinal studies are needed to determine potential causal relationships.

Neuromodulatory effects of transcranial electrical stimulation on emotion regulation in internalizing psychopathologies.

OBJECTIVE: We hypothesize offset theta-tACS (transcranial alternating current stimulation) improves emotion regulation (ER) and psychopathology more than transcranial direct current stimulation (tDCS) in participants with internalizing psychopathologies (IPs). METHODS: This pilot study utilized a double-blind, pseudo-counterbalanced, sham-controlled design with participants with IPs. Participants were assigned to receive tDCS or tACS, underwent four stimulation sessions (two sham), and completed an emotion regulation task (ERT) during or after stimulation. Participants completed the Beck Depression Inventory before/after the study, the Spielberger State and Trait Anxiety Index after each ERT, and rated their arousal, valence, and perceived reappraisal ability during the ERT. RESULTS: Participants receiving either stimulation type showed a reduction in anxiety, depression, and valence and arousal ratings. We additionally discovered an effect demonstrating those who received sham stimulation first displayed little-to-no change in any score across the study, but tACS participants who received verum stimulation first showed significant improvements in each metric. CONCLUSIONS: Improving ER capabilities via theta tACS has the potential to yield beneficial clinical effects. SIGNIFICANCE: This study adds validity to the use of non-invasive neuromodulatory methods, especially tACS, to alleviate IPs. Additional research is needed to better understand the effects of sham stimulation. Careful consideration of sham incorporation should be made in future studies.

Neural reactivity to affective stimuli and internalizing symptom dimensions in a transdiagnostic patient sample.

BACKGROUND: Internalizing psychopathologies (IPs) are highly comorbid and exhibit substantial overlap, such as aberrant affective reactivity. Neural reactivity to emotional images, measured via the late positive potential (LPP) event-related potential (ERP) component, has been utilized to index affective reactivity in IPs. The LPP is often examined in isolation with a specific disorder, ignoring overlap between IPs. The current study examined how transdiagnostic IP symptom dimensions relate to neural affective reactivity in a highly comorbid patient sample. METHODS: Participants (N = 99) completed a battery of IP symptom assessments as well as a target categorization task while viewing pleasant, unpleasant, and neutral images during electroencephalography recording. ERPs to each image valence were averaged from 400 to 1000 ms following picture onset at pooled centroparietal and occipital electrodes to calculate the LPP. A principal components analysis performed on the IP symptom measures resulted in two factors: affective distress/misery and fear-based anxiety. RESULTS: Fear-based anxiety was associated with enhanced LPP reactivity to unpleasant, but not pleasant, images. Distress/misery was related to attenuated average LPP reactivity across images. CONCLUSIONS: Results revealed a dissociable effect of IP symptom factors in a transdiagnostic sample such that enhanced reactivity to negative images was specific to enhanced fear-based anxiety symptoms while distress/misery symptoms predicted blunted affective reactivity. Neural affective reactivity may serve as an objective biological marker to elucidate the nature of psychological concerns in individuals with comorbid IPs.

Morning light treatment for traumatic stress: The role of amygdala reactivity study protocol.

BACKGROUND: Exposure to trauma can result in various mental health disorders including anxiety, depression, and posttraumatic stress disorder (PTSD). Although psychotherapies and pharmacotherapies exist for the treatment of these disorders, many individuals fail to receive treatment and among those who do, many remain symptomatic. Therefore, it is critical to continue developing new interventions for traumatic stress that target underlying mechanisms of pathology and offer a safe and acceptable alternative to current treatments. Morning light treatment has good potential as a novel non-invasive, low risk treatment for traumatic stress. Evidence suggests that morning light may improve traumatic stress by reducing reactivity in the amygdala, a brain region implicated in the pathophysiology of PTSD and anatomically linked to circadian photoreceptors in the eye. METHODS: In this study, we aim to establish a significant dose-response relationship between duration of morning light treatment and reduction in amygdala reactivity among individuals with traumatic stress symptoms (NCT# 04117347). Using a transdiagnostic approach, sixty-six individuals with a history of a DSM-5 criterion A trauma and traumatic stress symptoms will be recruited to participate in a 5-week study. Participants will be randomized across three treatment arms based on morning light treatment duration: 15-minutes, 30-minutes, or 60-minutes of light treatment per day for four weeks. To evaluate amygdala activity, participants will undergo fMRI at pre-treatment, mid-treatment, and post-treatment. Participants will also complete clinical assessments and self-report measures of PTSD, depression, and anxiety at pre-treatment, mid-treatment, and post-treatment. DISCUSSION: Morning light therapy may be an acceptable, feasible, and effective treatment for individuals suffering from traumatic stress. Identifying mechanistically relevant targets, and the doses needed to impact them, are critical steps in developing this new treatment approach for the sequelae of traumatic stress.

Electrocortical measures of win and loss processing are associated with mesocorticolimbic functional connectivity: A combined ERP and rs-fMRI study.

The reward positivity (RewP) event-related potential is a well-validated measure of reward processing implicated in internalizing psychopathologies. The RewP is thought to reflect reward reactivity in the mesocorticolimbic system; however, it is not clear how the RewP is related to the functional connectivity of reward-related brain regions. The current study examined associations between the RewP (Win and Loss residuals) and resting-state fMRI (rs-fMRI), among adults with internalizing psychopathology (IP) and healthy controls (HC). All participants (N = 102) completed a validated monetary reward task during electroencephalogram and rs-fMRI. Regression analyses were conducted with (1) RewP-Win residual amplitude and striatal seeds (caudate, putamen, nucleus accumbens) and (2) RewP-Loss residual amplitude and anterior cingulate cortex (ACC) seeds. Overall, individuals with greater RewP-Win residual amplitude demonstrated increased rs-fMRI connectivity between striatal regions and the medial prefrontal cortex, as well as the parahippocampal gyrus, but decreased connectivity between striatal regions and regions involved in cognitive control and sensorimotor processing. Greater RewP-Loss residual was related to greater connectivity between the ACC and regions involved in reward/loss processing and motor control, but decreased connectivity between the ACC and regions involved in cognitive control. Relationships between the RewP and rs-fMRI were generally consistent across IP and HC. However, a few patterns were unique to IP. Results indicate the RewP is associated with resting-state functional connectivity of reward- and loss-related brain regions, suggesting connectivity of the mesocorticolimbic system may be an important individual difference factor in dimensions of attainment of reward and loss.

Brain response to emotional faces in anxiety and depression: neural predictors of cognitive behavioral therapy outcome and predictor-based subgroups following therapy.

BACKGROUND: Neuroimaging studies have shown variance in brain response to emotional faces predicts cognitive behavioral therapy (CBT) outcome. An important next step is to determine if individual differences in neural predictors of CBT response represent distinct patient groups. METHODS: In total, 90 patients with internalizing disorders completed a face-matching task during functional magnetic resonance imaging before and after 12 weeks of CBT and 45 healthy controls completed the task before and after 12 weeks. Patients exhibiting a pre-to-post CBT >50% reduction in symptom severity on two measures were considered treatment responders. Regions of interest (ROIs) for angry, fearful, and happy faces were submitted to receiver operating characteristic (ROC) curve analysis. Significant ROIs were then submitted to decision tree analysis to classify responder/non-responder subgroups. Psychophysiological interactions (PPI) were used to explore functional connectivity in the region(s) that delineated subgroups. RESULTS: A total of 51 patients were treatment responders and ROC curve results were significant for all face types though specific regions varied. Decision tree results revealed superior occipital response to angry faces identified patient subgroups such that the subgroup with 'high' occipital activity had more responders than the 'low' occipital subgroup. Following CBT, the high, relative to low, occipital subgroup was less symptomatic. Controls exhibited stable superior occipital activation over time. Whole-brain PPI showed reduced baseline superior occipital-postcentral gyrus functional connectivity in responders compared to non-responders. CONCLUSIONS: Preliminary findings indicate patients characterized by relatively more pre-treatment superior occipital gyrus engagement to angry faces and reduced superior occipital-postcentral gyrus connectivity, relative to non-responders, may represent a phenotype likely to benefit from CBT.

Anterior cingulate cortex activation during attentional control as a transdiagnostic marker of psychotherapy response: a randomized clinical trial.

Anterior cingulate cortex (ACC) response during attentional control in the context of task-irrelevant emotional faces is a promising biomarker of cognitive behavioral therapy (CBT) outcome in patients with social anxiety disorder (SAD). However, it is unclear whether this biomarker extends to major depressive disorder (MDD) and is specific to CBT outcome. In the current study, 72 unmedicated patients with SAD (n = 39) or MDD (n = 33) completed a validated emotional interference paradigm during functional magnetic resonance imaging before treatment. Participants viewed letter strings superimposed on task-irrelevant threat and neutral faces under low perceptual load (high interference) and high perceptual load (low interference). Biomarkers comprised anatomy-based rostral ACC (rACC) and dorsal ACC (dACC) response to task-irrelevant threat (>neutral) faces under low and high perceptual load. Patients were randomly assigned to 12 weeks of CBT or supportive therapy (ST) (ClinicalTrials.gov identifier: NCT03175068). Clinician-administered measures of social anxiety and depression severity were obtained at baseline and every 2 weeks throughout treatment (7 assessments total) by an assessor blinded to the treatment arm. A composite symptom severity score was submitted to latent growth curve models. Results showed more baseline rACC activity to task-irrelevant threat>neutral faces under low, but not high, perceptual load predicted steeper trajectories of symptom improvement throughout CBT or ST. Post-hoc analyses indicated this effect was driven by subgenual ACC (sgACC) activation. Findings indicate ACC activity during attentional control may be a transdiagnostic neural predictor of general psychotherapy outcome.

Network Diffusion Embedding Reveals Transdiagnostic Subnetwork Disruption and Potential Treatment Targets in Internalizing Psychopathologies.

Network diffusion models are a common and powerful way to study the propagation of information through a complex system and they offer straightforward approaches for studying multimodal brain network data. We developed an analytic framework to identify brain subnetworks with perturbed information diffusion capacity using the structural basis that best maps to resting state functional connectivity and applied it towards a heterogeneous dataset of internalizing psychopathologies (IPs), a set of psychiatric conditions in which similar brain network deficits are found across the swath of the disorders, but a unifying neuropathological substrate for transdiagnostic symptom expression is currently unknown. This research provides preliminary evidence of a transdiagnostic brain subnetwork deficit characterized by information diffusion impairment of the right area 8BM, a key brain region involved in organizing a broad spectrum of cognitive tasks, which may underlie previously reported dysfunction of multiple brain circuits in the IPs. We also demonstrate that models of neuromodulation involving targeting this brain region normalize IP diffusion dynamics towards those of healthy controls. These analyses provide a framework for multimodal methods that identify both brain subnetworks with disrupted information diffusion and potential targets of these subnetworks for therapeutic neuromodulatory intervention based on previously well-characterized methodology.

Sleep quality and emotion recognition in individuals with and without internalizing psychopathologies.

BACKGROUND AND OBJECTIVES: Separate lines of research indicate sleep quality may impact recognition of facial expressions in anxious or depressed individuals. This study examined facial emotion recognition ability in the context of self-perceived sleep quality and anxiety and depression symptom levels in individuals with and without internalizing psychopathologies. METHODS: Seventy anxious and/or depressed patients and 24 demographically matched healthy controls completed the Pittsburgh Sleep Quality Index (PSQI), standard measures of anxiety and depression, and an Emotion Recognition Task comprising negative and positive facial expressions. RESULTS: Analyses of variance results revealed patients reported worse sleep quality than controls. Linear mixed-effects models indicated that all participants demonstrated better emotion recognition abilities in identifying positive versus negative emotions. For reaction time, but not accuracy, regression results revealed significant individual differences, with worse sleep quality predicting slower reaction times for positive faces, specifically for happiness. LIMITATIONS: The use of a subjective measure of sleep quality and a specific behavioral paradigm for emotion recognition may impact the generalizability of the findings. CONCLUSIONS: Associations between task performance and emotional valence of facial expression implies that poor sleep quality, beyond internalizing symptom severity, may disrupt emotion processing.

Anterior cingulate cortex activity during attentional control corresponds with rumination in depression and social anxiety.

Rumination and worry are transdiagnostic perseverative cognitions that have overlapping and distinct characteristics. While the mechanisms of perseverative cognitions remain incomplete, limited data indicate anterior cingulate cortex (ACC) as it relates to top-down functions contributes to perseverative cognitions in internalizing conditions. The current study extends this work in patients with major depression (n = 39) or social anxiety (n = 42). During fMRI, participants viewed images comprising letter strings superimposed on task-irrelevant threatening or neutral faces. To moderate task difficulty, there was a low perceptual load condition where the target letter was in a string of identical letters and high load condition with the target letter in a mixed letter string increasing task difficulty. Regions of interest (ROI) comprised dorsal ACC and rostral ACC. Bilateral amygdala was also examined. Results showed diagnostic groups had similar levels of rumination and worry. Exploratory hierarchical regression analysis comprising clinical measures, task performance, and the 4 ROIs revealed significantly less dorsal ACC engagement during low (vs. high) load to task-irrelevant faces corresponded with more rumination, but not worry, regardless of diagnostic status. However, the ACC finding did not survive Bonferroni correction. Preliminary results suggest dorsal ACC response during attentional control may serve as a transdiagnostic mechanism of rumination.

Neural mechanisms and predictors of SSRI and CBT treatment of anxiety: A randomized trial focused on emotion and cognitive processing.

Anxiety disorders (ADs) are common and difficult to treat. While research suggests ADs are characterized by an imbalance between bottom-up and top-down attention processes and that effective treatments work by correcting this dysfunction, there is insufficient data to explain how and for whom treatments work. The late positive potential (LPP), an event-related potential reflecting elaborative processing of motivationally salient stimuli, is sensitive to both bottom-up and top-down processes. The present study examines the LPP in healthy controls (HC) and patients with ADs under low and high working memory (WM) load to assess its utility as a predictor and index of symptom reduction in patients who underwent cognitive behavioral therapy (CBT) or selective serotonin reuptake inhibitor (SSRI) treatment. The LPP when viewing negative and neutral distractor images and WM performance were assessed in 96 participants (40 HC, 32 CBT, 24 SSRI) during a letter recall task at Week 0 and in a subset of the study sample (23 CBT, 16 SSRI) at Week 12. Patients were randomly assigned to twelve weeks of CBT or SSRI treatment. Participants completed self-reported symptom measures at each time point. Greater Week 0 LPP to negative images under low WM load predicted greater symptom reduction in the SSRI, but not the CBT, group. Regression analyses examining the LPP to negative images as an index of symptom reduction revealed a smaller decrease in the LPP to negative images under low WM load was associated with less anxiety reduction across treatment modalities. Findings suggest the LPP during low WM load may serve as a cost-effective predictor and index of treatment outcome in ADs. Clinical Trials Registration: ClinicalTrials.gov (Identifier: NCT01903447).

Individual differences in striatal and amygdala response to emotional faces are related to symptom severity in social anxiety disorder.

Social anxiety disorder (SAD) is a common heterogeneous disorder characterized by excessive fear and deficient positive experiences. Case-control emotion processing studies indicate that altered amygdala and striatum function may underlie SAD; however, links between these regions and symptomatology have yet to be established. Therefore, in the current study, 80 individuals diagnosed with SAD completed a validated emotion processing task during functional magnetic resonance imaging. Anatomy-based regions of interest were amygdala, caudate, putamen, and nucleus accumbens. Neural activity in response to angry > happy faces and fearful > happy faces in these regions were submitted to multiple linear regression analysis with bootstrapping. Additionally, multiple linear regression analysis was performed to explore clinical features of SAD. Results showed greater putamen activity and less amygdala activity in response to angry > happy faces were related to greater social anxiety severity. In the model consisting of caudate and amygdala activity in response to angry > happy faces, results were marginally related to social anxiety severity and the pattern of activity was similar to the regression model comprising putamen and amygdala. Nucleus accumbens activity was not related to social anxiety severity. There was no correspondence between brain activity in response to fearful > happy faces and social anxiety severity. Clinical variables revealed greater levels of anhedonia and general anxiety were related to social anxiety severity, however, neural activity was not related to these features of SAD. Neuroimaging findings suggest that variance in dorsal striatal and amygdala activity in response to certain social signals of threat contrasted with an approach/rewarding social signal may contribute to individual differences in SAD. Clinical findings indicate variance in anhedonia and general anxiety symptoms may contribute to individual differences in social anxiety severity.

Resting state functional connectivity correlates of rumination and worry in internalizing psychopathologies.

BACKGROUND: Rumination and worry are repetitive negative thinking (RNT) tendencies that contribute to the development and maintenance of internalizing psychopathologies. Accruing data suggest rumination and worry represent overlapping and unique transdiagnostic cognitive processes. Yet, prior neuroimaging research has mostly focused on rumination in depression, which points to involvement of resting-state brain activity in default mode, executive, salience, and/or affective networks. METHODS: The current study examined relations between brain activity during rest and RNT in a transdiagnostic sample. Resting-state fMRI data was analyzed in 80 unmedicated patients with internalizing conditions. Regression analysis, controlling for anxiety and depression symptoms, was performed with seed regions implicated in default mode, executive, salience, and affective networks. Rumination and worry were assessed with standard self-report measures. RESULTS: Whole-brain regression results showed more rumination and worry jointly corresponded with greater positive resting-state functional connectivity (rsFC) between the amygdala and prefrontal regions (i.e., middle frontal gyrus, inferior frontal gyrus). Conversely, more worry (controlling for rumination) corresponded with greater negative rsFC between amygdala and precuneus. No significant results were observed for rumination alone (controlling for worry). CONCLUSIONS: Findings indicate the affective network plays a role in RNT, and distinct patterns of connectivity between amygdala and regions implicated in the executive and default mode networks were observed across patients with internalizing conditions. Results suggest different mechanisms contribute to RNT as a unitary construct and worry as a unique construct.