Annual Research Review: Emotion processing in offspring of mothers with depression diagnoses - a systematic review of neural and physiological research.

BACKGROUND: Theories of the intergenerational transmission of depression emphasize alterations in emotion processing among offspring of depressed mothers as a key risk mechanism, raising questions about biological processes contributing to these alterations. The objective of this systematic annual research review was to examine and integrate studies of the associations between maternal depression diagnoses and offspring's emotion processing from birth through adolescence across biological measures including autonomic psychophysiology, electroencephalography (EEG), magnetoencephalography (MEG), event-related potentials (ERP), and structural and functional magnetic resonance imaging (MRI). METHODS: The review was conducted in accordance with the PRISMA 2020 standards. A systematic search was conducted in PsycInfo and PubMed in 2022 for studies that included, 1) mothers with and without DSM-defined depressive disorders assessed via a clinical or diagnostic interview, and 2) measures of offspring emotion processing assessed at the psychophysiological or neural level between birth and 18 years of age. RESULTS: Findings from 64 studies indicated that young offspring of mothers with depression histories exhibit heightened corticolimbic activation to negative emotional stimuli, reduced left frontal brain activation, and reduced ERP and mesocorticolimbic responses to reward cues compared to offspring of never-depressed mothers. Further, activation of resting-state networks involved in affective processing differentiate offspring of depressed relative to nondepressed mothers. Some of these alterations were only apparent among youth of depressed mothers exposed to negative environmental contexts or exhibiting current emotional problems. Further, some of these patterns were observable in infancy, reflecting very early emerging vulnerabilities. CONCLUSIONS: This systematic review provides evidence that maternal depression is associated with alterations in emotion processing across several biological units of analysis in offspring. We present a preliminary conceptual model of the role of deficient emotion processing in pathways from maternal depression to offspring psychopathology and discuss future research avenues addressing limitations of the existing research and clinical implications.

The interplay of childhood maltreatment and maternal depression in relation to the reward positivity in youth.

Guided by developmental psychopathology and dual-risk frameworks, the present study examined the interplay between childhood maltreatment and maternal major depression history in relation to neural reward responsiveness in youth. The sample consisted of 96 youth (ages 9-16; M = 12.29 years, SD = 2.20; 68.8% female) drawn from a large metropolitan city. Youth were recruited based on whether their mothers had a history of major depressive disorder (MDD) and were categorized into two groups: youth with mothers with a history of MDD (high risk; HR; n = 56) and youth with mothers with no history of psychiatric disorders (low risk; LR; n = 40). The reward positivity (RewP), an event-related potential component, was utilized to measure reward responsiveness and the Childhood Trauma Questionnaire measured childhood maltreatment. We found a significant two-way interaction between childhood maltreatment and risk group in relation to RewP. Simple slope analysis revealed that in the HR group, greater childhood maltreatment was significantly associated with reduced RewP. The relationship between childhood maltreatment and RewP was not significant among the LR youth. The present findings demonstrate that the association between childhood maltreatment and blunted reward responsiveness is dependent on whether offspring have mothers with histories of MDD.

Mega-analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group.

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

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.

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.

Development of Overgeneral Autobiographical Memory in Offspring of Depressed Mothers.

Maternal depression increases the risk for offspring cognitive vulnerabilities, which may be a mechanism underlying the intergenerational transmission of depression. Little is known about how cognitive vulnerabilities, particularly memory biases, develop in the offspring of depressed mothers. Understanding the etiology of memory biases may lead to novel intervention targets. Therefore, the current study examined the prospective impact of maternal depression on the development of offspring overgeneral autobiographical memory (OGM; i.e., the tendency to recall less specific memories), a cognitive vulnerability implicated in the intergenerational transmission of depression. Participants were offspring (ages 8-14; 51% daughters, 81% Caucasian) of mothers with (n= 129) or without (n= 122) a history of major depressive disorder (MDD) during the offspring's life. Mothers and offspring completed assessments every 6 months for 2 years. Compared to offspring of never-depressed mothers, offspring of mothers with a history of MDD recalled less specific memories in response to negative, but not positive, cue words at the initial assessment, and this bias was maintained across the 2-year follow-up. For offspring of depressed, but not never-depressed, mothers, higher levels of maternal depressive symptoms at a given assessment predicted prospective decreases in the children's autobiographical memory specificity. Again, this finding was specific to negative, but not positive, cue words. These results suggest that maternal depression has both short- and long-term effects on the development of offspring OGM to negative cues, which may represent a malleable cognitive vulnerability for the intergenerational transmission of MDD that could be targeted for intervention.

Risk for youth anxiety during the COVID-19 pandemic: The interactive impact of financial stress and prepandemic electrocortical reactivity to negative self-referential stimuli.

Despite evidence that stress exposure increases risk for internalizing symptoms in youth, it remains unclear which youth are most vulnerable. This study examined whether youth's prepandemic late positive potential (LPP), an electrocortical marker of sustained attention to affective stimuli, exacerbated the impact of stress on prospective increases in depression and anxiety symptoms from before to during the COVID-19 pandemic. Participants were 29 youth (ages 9-16, 82.8% girls) who completed depression and anxiety symptom measures and an affective words task to assess LPP to positive and negative self-referential stimuli prepandemic onset. Postpandemic onset, approximately 16.03 months (SD = 8.86) after their baseline assessments, youth again completed symptom measures as well as the UCLA Life Stress Interview to assess ongoing social and financial chronic stress. Results indicated a significant interaction between youth LPP to negative words and financial stress. Greater exposure to financial stress during the pandemic predicted greater anxiety symptom increases specifically for youth who demonstrated enhanced prepandemic LPP to negative words. Results were specific to the prediction of anxiety, but not depression, symptoms. If replicated in larger studies, findings highlight enhanced LPP to negative stimuli as a promising target for intervention for youth exposed to greater financial stress.

The effects of rumination on internalising symptoms in the context of the COVID-19 pandemic among mothers and their offspring: a brief report.

As a result of the novel coronavirus (COVID-19) pandemic, anxiety and depressive symptoms have risen among children and adults. However, it remains unclear why the effects of the pandemic are so salient for certain individuals. This study examined rumination, a well-established risk factor for internalising disorders, as a predictor of prospective increases in anxiety and depression symptoms in mothers and their offspring. Change in rumination during the pandemic was also examined as a predictor of symptom transmission at the dyadic level. Fifty-three biological mother-child dyads were recruited from two longitudinal studies that had completed their respective baselines prior to the COVID-19 pandemic. Mothers and youth (ages 9-15 years, 77.4% female) completed measures of depression and anxiety symptoms and rumination before and during the pandemic. Results revealed baseline rumination was positively associated with internalising symptom changes for mothers, but not youth. Moreover, pre-to-peri pandemic changes in rumination were associated with prospective increases in mother and youth internalising symptoms. Finally, results revealed a significant correlation for pre-to-peri pandemic depressive symptom change among mothers and youth; however, rumination did not mediate this association. Findings highlight changes in rumination as a potential mechanism for internalising symptom risk during the COVID-19 pandemic across development.

Differences in cortical thinning across development among individuals with and without anxiety disorders.

BACKGROUND: Anxiety is associated with aberrant patterns of cortical thickness in regions implicated in emotion regulation. However, few studies have examined cortical thickness differences between individuals with anxiety and healthy controls (HCs) across development, particularly during childhood when cortical thinning begins and anxiety risk increases. A better understanding of age-related changes in cortical thickness patterns among anxious individuals is essential to develop plausible targets for early identification. METHODS: The current study examined how age impacted differences in cortical thickness patterns between HCs and anxious individuals. Participants included 233 individuals (ages 7-35) with a current anxiety disorder (n = 149) or no lifetime history of psychopathology (n = 84). Cortical thickness of regions that are implicated in emotion regulation (ventromedial prefrontal cortex [vmPFC], rostral anterior cingulate [rACC], and insula) were assessed. RESULTS: All regions showed significant thinning with age, except left rACC and right insula. However, rates of thinning differed among anxious and HC participants, with anxious participants demonstrating slower rates of right vmPFC thinning. Regions of significance analyses indicated that anxious, relative to HC, participants exhibited thinner right vmPFC before age 11, but thicker right vmPFC after age 24. CONCLUSIONS: Current findings suggest that anxious individuals do not demonstrate normative right vmPFC cortical thinning, which may lead them to exhibit both thinner vmPFC in middle childhood and thicker vmPFC in adulthood compared with HCs. These findings may provide plausible targets for identification of anxiety risk that differ based on developmental stage.

The moderating role of externalizing problems on the association between anxiety and the error-related negativity in youth.

The error-related negativity (ERN) is an event-related potential that reflects error monitoring. Enhanced ERN indicates sensitivity to performance errors and is a correlate of anxiety disorders. In contrast, youth with externalizing problems exhibit a reduced ERN, suggesting decreased error monitoring. Anxiety and externalizing problems commonly co-occur in youth, but no studies have tested how comorbidity might modulate the ERN. In a sample of youth (N = 46, ages 7-19) with and without anxiety disorders, this preliminary study examined the interactive effect of anxiety and externalizing problems on ERN. Results suggest that externalizing problems moderate the relation between anxiety symptoms and ERN in youth. Anxious youth with less externalizing problems exhibited enhanced ERN response to errors. Conversely, anxious youth with greater externalizing problems demonstrated diminished ERN in response to errors. The regions of significance and proportion affected tests indicated that the moderating the effect of externalizing problems was only significant for youth with anxiety disorders. Findings suggest that enhanced neural error sensitivity could be a specific neurophysiological marker for anxiety disorders, whereas anxious individuals with comorbid externalizing problems demonstrate reduced error monitoring, similar to those with primary externalizing pathology. Results underscore the utility of examining neural correlates of pediatric anxiety comorbidity subtypes.

24-Month Outcomes of Primary Care Web-Based Depression Prevention Intervention in Adolescents: Randomized Clinical Trial.

BACKGROUND: Adolescent depression carries a high burden of disease worldwide, but access to care for this population is limited. Prevention is one solution to curtail the negative consequences of adolescent depression. Internet interventions to prevent adolescent depression can overcome barriers to access, but few studies examine long-term outcomes. OBJECTIVE: This study compares CATCH-IT (Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training), an internet-based intervention, to a general health education active control for depression onset at 12 and 24 months in adolescents presenting to primary care settings. METHODS: A 2-site randomized trial, blinded to the principal investigators and assessors, was conducted comparing Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training to health education to prevent depressive episodes in 369 adolescents (193 youths were randomly assigned to Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training and 176 to health education) with subthreshold depressive symptoms or prior depressive episodes. Participants were recruited from primary care settings in the United States. The primary outcome was the occurrence of a depressive episode, determined by the Depression Symptom Rating. The secondary outcome was functioning, measured by the Global Assessment Scale. RESULTS: In intention-to-treat analyses, the adjusted hazard ratio favoring Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training for first depressive episode was not statistically significant at 12 months (hazard ratio 0.77, 95% CI 0.42-1.40, P=.39) and 24 months (hazard ratio 0.87, 95% CI 0.52-1.47, P=.61). Competent Adulthood Transition with Cognitive Behavioral Humanistic and Interpersonal Training provided preventive benefit for first depressive episode for those with mild hopelessness or at least moderate paternal monitoring at baseline. Global Assessment Scale scores improved comparably in both groups (intention-to-treat). CONCLUSIONS: A technology-based intervention for adolescent depression prevention implemented in primary care did not have additional benefit at 12 or 24 months. Further research is necessary to determine whether internet interventions have long-term benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT01893749; http://clinicaltrials.gov/ct2/show/NCT01893749.

The roles of early-life adversity and rumination in neural response to emotional faces amongst anxious and depressed adults.

BACKGROUND: Early-life adversity (ELA) is a risk factor for internalizing psychopathology (IP). ELA is also linked to alterations in neural phenotypes of emotion processing and maladaptive emotion regulatory strategies, such as ruminative brooding, in adulthood. We therefore expected that ELA would predict cortical brain activation to emotional faces in transdiagnostic IP and in turn, mediate the extent of rumination amongst patients with IPs and ELA (IP + ELA). METHOD: One hundred and thirty-two individuals, including 102 treatment-seeking adults with heterogeneous IPs and 30 healthy controls (HCs) performed an Emotional Face-Matching Task during functional magnetic resonance imaging. Whole-brain analyses compared HC (n = 30), IP (n = 52), and IP + ELA (n = 50) neural responses to emotional (angry, fearful, happy, and sad) faces v. shapes, controlling for depression and anxiety symptoms. Parameter estimates of activation were extracted for significant between-group differences and tested as a mediator of ruminative brooding in IP + ELA. RESULTS: IP + ELA demonstrated increased activation in the superior frontal gyrus and anterior cingulate cortex (fear), superior parietal lobule, precuneus, posterior cingulate, and inferior temporal gyrus (fear only), and cuneus (fear and angry). These regions were preferentially correlated with ruminative brooding in IP + ELA, many of which mediated the link between IP + ELA and ruminative brooding. CONCLUSIONS: Results provide evidence that ELA history amongst IP patients augments engagement of brain regions involved in emotion processing, above and beyond what is accounted for by current symptoms. Though longitudinal designs are needed, alterations in the neural correlates of maladaptive processing of socio-emotional information may be a common pathway by which ELA poses risk for psychopathology.

Developmental changes in resting-state functional networks among individuals with and without internalizing psychopathologies.

BACKGROUND: Three well-established intrinsic connectivity networks (ICNs) involved in cognitive-affective processing include the cognitive control network (CCN), default mode network (DMN), and salience and emotional network (SEN). Despite recent advances in understanding developmental changes in these ICNs, the majority of research has focused on single seeds or networks in isolation with limited age ranges. Additionally, although internalizing psychopathologies (IPs), such as anxiety and depression, are often characterized by maladaptive cognitive-affective processing styles, it is not clear how IP history influences age-related changes in brain networks. METHOD: The current study aimed to characterize the normative development of the CCN, DMN, and SEN across a large age-span (7-29 year olds) of typically developing (TD) individuals (n = 97). We also explore how age may impact differences in network connectivity between TD individuals and patients with IPs (n = 136). RESULTS: Among TD individuals, DMN and CCN connectivity strengthened with age, whereas connectivity between the SEN and ventromedial prefrontal cortex weakened across development. When exploring group (IP vs. TD) differences, the IP group was characterized by greater connectivity between the CCN and cerebellum and between the SEN and caudate from childhood to early adulthood, relative to TD individuals. In addition, patients with IPs, versus TD individuals, exhibited reduced connectivity between the SEN and medial frontal gyrus from adolescence to adulthood. CONCLUSIONS: The current findings shed light on differential age-related changes in brain network patterns among psychiatrically free, TD individuals and those with internalizing disorders, and may provide plausible targets for novel mechanism-based treatments that differ based on developmental stage.

Age differences in electrocortical reactivity to fearful faces following aversive conditioning in youth.

Although biases in the processing of affectively salient stimuli are thought to increase risk for psychopathology across the lifespan, questions remain regarding how these biases develop. The current study tested an aversive conditioning model for the development of children's sensitivity in detecting fearful faces at varying levels of emotional intensity and their facilitated attention to fearful faces assessed via the late positive potential (LPP) event-related potential component. Participants (N = 144, ages 7-11 years) were randomly assigned to one of three conditions: an active training condition in which an 85-dB white noise burst was paired with fearful faces, an active control condition in which the white noise was presented randomly throughout the task, and a no-sound condition. Children completed a separate task in which they viewed happy, sad, and fearful child faces at varying levels of emotional intensity while electroencephalography (EEG) was recorded. Although there were no conditioning group differences in children's sensitivity in detecting facial displays of emotion, there were group differences in LPP magnitude that were moderated by children's age. Among younger children, those in the active conditioning group exhibited smaller LPP amplitudes to high-intensity fearful faces than children in the control groups. However, among older youth, those in the active conditioning group exhibited larger LPP amplitudes to high-intensity fearful faces than children in the control groups. These findings provide insight into how attentional biases may develop in children and how period of development may influence these patterns.

Impact of pubertal timing and depression on error-related brain activity in anxious youth.

Anxiety disorders are associated with enhanced error-related negativity (ERN) across development but it remains unclear whether alterations in brain electrophysiology are linked to the timing of puberty. Pubertal timing and alterations of prefrontal and limbic development are implicated in risk for depression, but the interplay of these factors on the ERN-anxiety association has not been assessed. We examined the unique and interactive effects of pubertal timing and depression on the ERN in a sample of youth 10-19 years old with anxiety disorders (n = 30) or no history of psychopathology (n = 30). Earlier pubertal maturation was associated with an enhanced ERN. Among early, but not late maturing youth, higher depressive symptoms were associated with a reduced ERN. The magnitude of neural reactivity to errors is sensitive to anxiety, depression, and development. Early physical maturation and anxiety may heighten neural sensitivity to errors yet predict opposing effects in the context of depression.

Neural correlates of rumination in adolescents with remitted major depressive disorder and healthy controls.

The aim of the present study was to use fMRI to examine the neural correlates of engaging in rumination among a sample of remitted depressed adolescents, a population at high risk for future depressive relapse. A rumination induction task was used to assess differences in the patterns of neural activation during rumination versus a distraction condition among 26 adolescents in remission from major depressive disorder (rMDD) and in 15 healthy control adolescents. Self-report depression and rumination, as well as clinician-rated depression, were also assessed among all participants. All of the participants recruited regions in the default mode network (DMN), including the posterior cingulate cortex, medial prefrontal cortex, inferior parietal lobe, and medial temporal gyrus, during rumination. Increased activation in these regions during rumination was correlated with increased self-report rumination and symptoms of depression across all participants. Adolescents with rMDD also exhibited greater activation in regions involved in visual, somatosensory, and emotion processing than did healthy peers. The present findings suggest that during ruminative thought, adolescents with rMDD are characterized by increased recruitment of regions within the DMN and in areas involved in visual, somatosensory, and emotion processing.

Increased pupil dilation to angry faces predicts interpersonal stress generation in offspring of depressed mothers.

BACKGROUND: Interpersonal stress generation is one mechanism hypothesized to increase risk for the intergenerational transmission of depression. Although there is some evidence of stress generation in offspring of depressed mothers, specific predictors of stress generation in these youth remain unknown. The goal of this study was to examine a peripheral measure of cognitive-affective reactivity (i.e. pupil dilation) to emotional interpersonal stimuli as a predictor of stress generation in offspring of depressed mothers. METHOD: The study included 129 mothers and their offspring (ages 8-15) recruited from the community who participated at two time points separated by 6 months. Youth's average pupil dilation to emotional faces (angry, happy, sad) as well as maternal lifetime history of major depressive disorder were assessed at baseline. In addition, both time points included assessments of youth's levels of self-generated (dependent) and independent episodic life stress in the preceding 6 months. RESULTS: Youth's pupil dilation to angry, but not sad or happy, faces predicted prospective increases in dependent interpersonal stress across the follow-up. This effect was only observed in offspring of depressed mothers and was not seen in offspring of never-depressed mothers. CONCLUSIONS: This study highlights a potential risk factor (heightened reactivity to facial displays of anger) that may identify which offspring of depressed mothers are at greatest risk for interpersonal stress generation.

Neural correlates of explicit and implicit emotion processing in relation to treatment response in pediatric anxiety.

BACKGROUND: Approximately 40%-45% of youth with anxiety disorders do not achieve remission (or a substantial reduction in symptoms) following treatment, highlighting the need to identify predictors of treatment response. Given the well-established link between attentional biases and anxiety disorders in youth and adults, this study examined the neural correlates of directing attention toward and away from emotional faces in relation to pediatric anxiety treatment response. METHOD: Prior to beginning treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline or cognitive behavior therapy (CBT), 37 youth (age 7-19 years) with generalized and/or social anxiety disorder completed a task with conditions that manipulated whether participants were instructed to match emotional faces (explicit emotion processing) or match shapes in the context of emotional face distractors (implicit emotion processing) during functional magnetic resonance imaging. RESULTS: Results revealed that reduced activation in superior frontal gyrus (SFG), encompassing the dorsal anterior cingulate cortex (ACC) and dorsomedial prefrontal cortex (PFC), during implicit processing of emotional faces predicted a greater reduction in anxiety severity pre-to-post treatment. Post hoc analyses indicated that effects were not significantly moderated by the type of treatment or anxiety type. CONCLUSIONS: Findings suggest that less recruitment of SFG, including the dorsal ACC and dorsomedial PFC, during implicit emotion processing predicts a greater reduction in youth anxiety symptoms pre-to-post treatment. Youth who exhibit reduced activation in these areas while matching shapes in the context of emotional face distractors may have more to gain from CBT and SSRI treatment due to preexisting deficits in attentional control. These findings suggest that neuroimaging may be a useful tool for predicting which youth are most likely to benefit from anxiety treatment.

Error-related brain activity and internalizing disorder symptom dimensions in depression and anxiety.

BACKGROUND: Research suggests that enhanced neural reactivity to errors, measured via the error-related negativity (ERN), is relatively unique to internalizing psychopathologies (IPs) and symptom clusters characterized by excessive worry and apprehension. However, no prior study has tested the association between the ERN and IP symptom dimensions in a heterogeneous, clinically representative patient population. The current study was designed to address this gap in the literature and clarify the role of the ERN in an adult IP treatment-seeking patient sample. METHOD: Eighty-five participants completed a well-validated flanker task known to robustly elicit the ERN and a battery of questionnaires assessing a range of IP symptoms. All participants had at least one IP diagnosis and over 75% had co-occurring IPs. A principal components analysis (PCA) was performed on the questionnaire data indicating two distinct factors that characterized the IP sample: affective distress/misery and fear-based anxiety. RESULTS: Analyses indicated that within this sample, an enhanced ERN, but not CRN, was associated with greater fear-based anxiety symptoms but had no relation with distress/misery symptoms. CONCLUSIONS: Together, these findings indicate that an enhanced ERN may not be specific to worry/apprehension and may extend to the IP fear dimension. The results also converge with a broader literature suggesting that fear-based psychopathology is characterized by an exaggerated reactivity to threat and this objective, psychophysiological response tendency may distinguish fear disorders from distress.

NEURAL REACTIVITY TO REWARD AS A PREDICTOR OF COGNITIVE BEHAVIORAL THERAPY RESPONSE IN ANXIETY AND DEPRESSION.

BACKGROUND: Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety and depression; however, response to CBT is heterogeneous across patients and many remain symptomatic after therapy, raising the need to identify prospective predictors for treatment planning. Altered neural processing of reward has been implicated in both depression and anxiety, and improving hedonic capacity is a goal of CBT. However, little is known about how neural response to reward relates to CBT outcomes in depression and anxiety. The current study used the reward positivity (RewP) event-related potential (ERP) component to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression (n = 30) and comorbid anxiety and depression (CAD, n = 22). METHODS: Participants completed a guessing reward ERP paradigm before completing 12 weeks of standard CBT. RESULTS: The majority of the sample (68%; 35 out of 52 patients) responded to treatment, and those with a reduced RewP at baseline were more likely to respond to treatment. A reduced RewP was also associated with a greater pre-to-post CBT reduction in depressive symptoms among individuals with CAD, but not among individuals with pure anxiety. CONCLUSIONS: CBT may be most beneficial in reducing depressive symptoms for individuals who demonstrate decreased reward reactivity prior to treatment. CBT may target reward brain function, leading to greater improvement in symptoms. These effects may be strongest, and therefore most meaningful, for individuals with reward-processing deficits prior to treatment.