Neurocognitive risk phenotyping to predict mood symptoms in adolescence.

Predicting mood disorders in adolescence is a challenge that motivates research to identify neurocognitive predictors of symptom expression and clinical profiles. This study used machine learning to test whether neurocognitive variables predicted future manic or anhedonic symptoms in two adolescent samples risk-enriched for lifetime mood disorders (Sample 1, n = 73, ages = 13-25, M [SD] = 19.22 [2.49] years, 68% lifetime mood disorder) or familial mood disorders (Sample 2, n = 154, ages = 13-21, M [SD] = 16.46 [1.95] years, 62% first-degree family history of mood disorder). Participants completed cognitive testing and functional magnetic resonance imaging at baseline, for behavioral and neural measures of reward processing and executive functioning. Next, participants completed a daily diary procedure for 8-16 weeks. Penalized mixed-effects models identified neurocognitive predictors of future mood symptoms and stress-reactive changes in mood symptoms. Results included the following. In both samples, adolescents showing ventral corticostriatal reward hyposensitivity and lower reward performance reported more severe stress-reactive anhedonia. Poorer executive functioning behavior was associated with heightened anhedonia overall in Sample 1, but lower stress-reactive anhedonia in both samples. In Sample 1, adolescents showing ventral corticostriatal reward hypersensitivity and poorer executive functioning reported more severe stress-reactive manic symptoms. Clustering analyses identified, and replicated, five neurocognitive subgroups. Adolescents characterized by neural or behavioral reward hyposensitivities together with average-to-poor executive functioning reported unipolar symptom profiles. Adolescents showing neural reward hypersensitivity together with poor behavioral executive functioning reported a bipolar symptom profile (Sample 1 only). Together, neurocognitive phenotypes may hold value for predicting symptom expression and profiles of mood pathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Mood Symptom Dimensions and Developmental Differences in Neurocognition in Adolescence.

Adolescence is critical period of neurocognitive development as well as increased prevalence of mood pathology. This cross-sectional study replicated developmental patterns of neurocognition and tested whether mood symptoms moderated developmental effects. Participants were 419 adolescents (n=246 with current mood disorders) who completed reward learning and executive functioning tasks, and reported on age, puberty, and mood symptoms. Structural equation modeling revealed a quadratic relationship between puberty and reward learning performance that was moderated by symptom severity: in early puberty, adolescents reporting higher manic symptoms exhibited heightened reward learning performance (better maximizing of rewards on learning tasks), whereas adolescents reporting elevated anhedonia showed blunted reward learning performance. Models also showed a linear relationship between age and executive functioning that was moderated by manic symptoms: adolescents reporting higher mania showed poorer executive functioning at older ages. Findings suggest neurocognitive development is altered in adolescents with mood pathology and suggest directions for longitudinal studies.

How can neurobiology of fear extinction inform treatment?

The neurobiology of extinction learning has been translated to inform the delivery of exposure therapy, the gold-standard treatment for fear and anxiety disorders. The inhibitory retrieval model suggests that extinction leads to the formation of a new inhibitory memory which competes with the original fear memory that remains intact, resulting in potential return of fear over time and across different contexts. Implications for exposure therapy include behavioral and pharmacological strategies to 1) maximize prediction error through expectancy violation, and 2) enhance consolidation, generalization, and retrievability of extinction learning. Yet, not all individuals respond to treatment. In order to enhance the effectiveness and durability of exposure-based treatments, future research on reward processing, stimulus valuation, and decision-making is needed. Understanding the complex relationships among threat, reward, and cognitive processes holds promise for developing personalized treatments to meet the needs of individuals with fear and anxiety disorders.

General and Specific Dimensions of Mood Symptoms Are Associated With Impairments in Common Executive Function in Adolescence and Young Adulthood.

Both unipolar and bipolar depression have been linked with impairments in executive functioning (EF). In particular, mood symptom severity is associated with differences in common EF, a latent measure of general EF abilities. The relationship between mood disorders and EF is particularly salient in adolescence and young adulthood when the ongoing development of EF intersects with a higher risk of mood disorder onset. However, it remains unclear if common EF impairments have associations with specific symptom dimensions of mood pathology such as blunted positive affect, mood instability, or physiological arousal, or if differences in common EF more broadly relate to what is shared across various symptom domains, such as general negative affect or distress. To address this question, bifactor models can be applied to simultaneously examine the shared and unique contributions of particular mood symptom dimensions. However, no studies to our knowledge have examined bifactor models of mood symptoms in relation to measures of common EF. This study examined associations between common EF and general vs. specific symptom dimensions (anhedonia, physiological arousal, and mania) using structural equation modeling in adolescents and young adults with varying severity of mood symptoms (n = 495, ages = 13-25 years, 68.69% female). A General Depression factor capturing shared variance across symptoms statistically predicted lower Common EF. Additionally, a factor specific to physiological arousal was associated with lower Common EF. Anhedonia-specific and Mania-specific factors were not significantly related to Common EF. Altogether, these results indicate that deficits in common EF are driven by, or reflect, general features of mood pathology that are shared across symptom dimensions but are also specifically associated with physiological arousal.

Rating expectations can slow aversive reversal learning.

The process of learning allows organisms to develop predictions about outcomes in the environment, and learning is sensitive to both simple associations and higher order knowledge. However, it is unknown whether consciously attending to expectations shapes the learning process itself. Here, we directly tested whether rating expectations shapes arousal during classical conditioning. Participants performed an aversive learning paradigm wherein one image (CS+) was paired with shock on 50% of trials, while a second image (CS-) was never paired with shock. Halfway through the task, contingencies reversed. One group of participants rated the probability of upcoming shock on each trial, while the other group made no online ratings. We measured skin conductance response (SCR) evoked in response to the CS and used traditional analyses as well as quantitative models of reinforcement learning to test whether rating expectations influenced arousal and aversive reversal learning. Participants who provided online expectancy ratings displayed slower learning based on a hybrid model of adaptive learning and reduced reversal of SCR relative to those who did not rate expectations. Mediation analysis revealed that the effect of associative learning on SCR could be fully explained through its effects on subjective expectancy within the group who provided ratings. This suggests that the act of rating expectations reduces the speed of learning, likely through changes in attention, and that expectations directly influence arousal. Our findings indicate that higher order expectancy judgments can alter associative learning.

Psychological Treatments for Anhedonia.

Anhedonia, a loss of interest or pleasure in activities, is a transdiagnostic symptom that characterizes many individuals suffering from depression and anxiety. Most psychological interventions are designed to decrease negative affect rather than increase positive affect, and are largely ineffective for reducing anhedonia. More recently, affective neuroscience has been leveraged to inform treatments for anhedonia by targeting aspects of the Positive Valence Systems, including impairments in reward anticipation, reward responsiveness, and reward learning. In this chapter, we review the efficacy of treatments and, when possible, highlight links to reward constructs. Augmented behavioral approaches and targeted cognitive interventions designed to target reward anticipation, responsiveness, and learning show preliminary efficacy in reducing anhedonia, while there is a relative lack of treatments that target positive emotion regulation and reward devaluation. In addition to developing treatments that address these targets, the field will benefit from establishing standardized measurement of anhedonia across units of analysis, mapping mechanisms of change onto aspects of reward processing, and examining anhedonia outcomes in the long-term.

Behavioral mediators of stress-related mood symptoms in adolescence & young adulthood.

BACKGROUND: Stress is a risk factor for unipolar and bipolar mood disorders, but the mechanisms linking stress to specific symptoms remain elusive. Behavioral responses to stress, such as impulsivity and social withdrawal, may mediate the associations between stress and particular mood symptoms. METHODS: This study evaluated behavioral mediators of the relationship between self-reported intensity of daily stress and mood symptoms over up to eight weeks of daily diary surveys. The sample included individuals with unipolar or bipolar disorders, or with no psychiatric history (n = 113, ages 15-25). RESULTS: Results showed that higher daily stress was related to higher severity of mania, and this pathway was mediated by impulsive behaviors. Higher stress also predicted higher severity of anhedonic depression, and social withdrawal mediated this relationship. A k-means clustering analysis revealed six subgroups with divergent profiles of stress-behavior-symptom pathways. LIMITATIONS: Given the observational study design, analyses cannot determine causal relationships amongst these variables. Further work is needed to determine how relationships between these variables may vary based on stressor type, at different timescales, and within different populations. CONCLUSIONS: Findings support a theoretical model in which impulsivity and social withdrawal act as behavioral mediators of the relationship between stress and mood symptoms. Additionally, distinct patterns of reactivity distinguished subgroups of people vulnerable to particular types of mood symptoms. These results provide novel information about how stress-reactive behaviors relate to specific mood symptoms, which may have clinical relevance as targets of intervention.

Changes in functional connectivity with cognitive behavioral therapy for social anxiety disorder predict outcomes at follow-up.

Approximately half of individuals with Social Anxiety Disorder (SAD) treated with psychological intervention do not achieve clinically significant improvement or retain long-term gains. Neurobiological models of SAD propose that disruptions in functioning of amygdala-prefrontal circuitry is implicated in short-term treatment response. However, whether treatment-related changes in functional connectivity predict long-term well-being after psychotherapy is unknown. Patients with SAD completed an incidental emotion regulation task during fMRI before and after treatment with cognitive behavioral therapy or acceptance and commitment therapy (n = 23, collapsed across groups). Psychophysiological interaction analyses using amygdala seed regions were conducted to assess changes in functional connectivity from pre-to post-treatment that predicted symptom change from 6 to 12-month follow-up. Negative change (i.e., greater inverse/weaker positive) in amygdala connectivity with the dorsomedial prefrontal cortex (dmPFC) and dorsal anterior cingulate cortex (dACC) predicted greater symptom reduction during follow-up. Positive change in amygdala connectivity with the cerebellum, fusiform gyrus, and pre-central and post-central gyri predicted less symptom reduction (e.g., no change or worsening). Results suggest that strengthened amygdala connectivity with regulatory regions may promote better long-term outcomes, whereas changes with visual and sensorimotor regions may represent sensitization to emotion-related cues, conferring poorer outcomes. Clinical implications for treatment personalization are discussed, should effects replicate in larger samples.

Positive and Negative Emotion Regulation in Adolescence: Links to Anxiety and Depression.

Emotion regulation skills develop substantially across adolescence, a period characterized by emotional challenges and developing regulatory neural circuitry. Adolescence is also a risk period for the new onset of anxiety and depressive disorders, psychopathologies which have long been associated with disruptions in regulation of positive and negative emotions. This paper reviews the current understanding of the role of disrupted emotion regulation in adolescent anxiety and depression, describing findings from self-report, behavioral, peripheral psychophysiological, and neural measures. Self-report studies robustly identified associations between emotion dysregulation and adolescent anxiety and depression. Findings from behavioral and psychophysiological studies are mixed, with some suggestion of specific impairments in reappraisal in anxiety. Results from neuroimaging studies broadly implicate altered functioning of amygdala-prefrontal cortical circuitries, although again, findings are mixed regarding specific patterns of altered neural functioning. Future work may benefit from focusing on designs that contrast effects of specific regulatory strategies, and isolate changes in emotional regulation from emotional reactivity. Approaches to improve treatments based on empirical evidence of disrupted emotion regulation in adolescents are also discussed. Future intervention studies might consider training and measurement of specific strategies in adolescents to better understand the role of emotion regulation as a treatment mechanism.