Striatal reactivity during emotion and reward relates to approach-avoidance conflict behaviour and is altered in adults with anxiety or depression.

BACKGROUND: We have previously reported activation in reward, salience and executive control regions during functional MRI (fMRI) using an approach-avoidance conflict (AAC) decision-making task with healthy adults. Further investigations into how anxiety and depressive disorders relate to differences in neural responses during AAC can inform their understanding and treatment. We tested the hypothesis that people with anxiety or depression have altered neural activation during AAC. METHODS: We compared 118 treatment-seeking adults with anxiety or depression and 58 healthy adults using linear mixed-effects models to examine group-level differences in neural activation (fMRI) during AAC decision-making. Correlational analyses examined relationships between behavioural and neural measures. RESULTS: Adults with anxiety or depression had greater striatal engagement when reacting to affective stimuli (p = 0.008, d = 0.31) regardless of valence, and weaker striatal engagement during reward feedback (p = 0.046, d = -0.27) regardless of the presence of monetary reward. They also had blunted amygdala activity during decision-making (p = 0.023, d = -0.32) regardless of the presence of conflict. Across groups, approach behaviour during conflict decision-making was inversely correlated with striatal activation during affective stimuli (p < 0.001, r = -0.28) and positively related to striatal activation during reward feedback (p < 0.001, r = 0.27). LIMITATIONS: Our transdiagnostic approach did not allow for comparisons between specific anxiety disorders, and our cross-sectional approach did not allow for causal inference. CONCLUSION: Anxiety and depression were associated with altered neural responses to AAC. Findings were consistent with the role of the striatum in action selection and reward responsivity, and they point toward striatal reactivity as a future treatment target. Blunting of amygdala activity in anxiety or depression may indicate a compensatory response to inhibit affective salience and maintain approach.

Differential associations of parental harshness and parental disengagement with overall cortisol output at 15 years: Implications for adolescent mental health.

Psychosocial stress in childhood and adolescence is linked to stress system dysregulation, although few studies have examined the relative impacts of parental harshness and parental disengagement. This study prospectively tested whether parental harshness and disengagement show differential associations with overall cortisol output in adolescence. Associations between overall cortisol output and adolescent mental health problems were tested concurrently. Adolescents from the Fragile Families and Child Wellbeing Study (FFCWS) provided hair samples for cortisol assay at 15 years (N = 171). Caregivers reported on parental harshness and disengagement experiences at 1, 3, 5, 9, and 15 years, and adolescents reported at 15 years. Both parent and adolescent reported depressive and anxiety symptoms and antisocial behaviors at 15. Greater parental harshness from 1-15 years, and harshness reported at 15 years in particular, was associated with higher overall cortisol output at 15. Greater parental disengagement from 1-15 years, and disengagement at 1 year specifically, was associated with lower cortisol output. There were no significant associations between cortisol output and depressive symptoms, anxiety symptoms, or antisocial behaviors. These results suggest that the unique variances of parental harshness and disengagement may have opposing associations with cortisol output at 15 years, with unclear implications for adolescent mental health.

Childhood maltreatment and within-person associations between cortisol and affective experience.

Glucocorticoids exert profound effects on the brain and behavior, but cortisol concentrations are rarely linked to subjectively reported emotional states in humans. This study examined whether the link between cortisol and subjective anxiety varied by childhood maltreatment history. To do this, 97 individuals (60.8% female) participated in a standardized stress task in the laboratory (Trier Social Stress Test, TSST) while providing serial ratings of their feelings of anxiety as well as cortisol samples in blood. These measurements were collected nine times across the laboratory visit, from immediately before the TSST to 65 minutes after stress initiation. We estimated the within-person association between cortisol concentrations and momentary feelings of anxiety for individuals with and without exposure to childhood maltreatment, measured via self-report on the Childhood Trauma Questionnaire (CTQ). Individuals exposed to maltreatment during childhood reported the greatest feelings of anxiety when cortisol concentrations were lowest. This pattern was exaggerated among female participants, those with posttraumatic stress disorder (PTSD), and those exposed to emotional neglect relative to other forms of maltreatment. Early life adversity, such as parental maltreatment, may alter the role of cortisol in affective experiences. This observation may provide preliminary, translational evidence of a novel pathway through which stress may lead to and maintain internalizing symptoms in humans. More studies accounting for the moderating role of childhood maltreatment in biobehavioral pathways are needed.

Violence Victimization Predicts Body Mass Index One Decade Later among an Urban Sample of African American Young Adults: Sex as a Moderator and Dehydroepiandrosterone as a Mediator.

Psychological stressors such as violence victimization are known contributors to obesity. However, moderators and mediators of this association have not been studied, although they might offer pathways for intervention or prevention. Using a sample of African American young adults, this study tested: (1) the moderating effect of sex on the effect of violence victimization on trajectories of body mass index (BMI), and (2) the mediating effect of dehydroepiandrosterone (DHEA) on this association. This 13-year longitudinal study followed 73 male and 80 female African American young adults who lived in an urban area from 1999 to 2012 when the youth were 20-32 years old. The independent variable was violence victimization measured in 1999 and 2000. The dependent variable was BMI measured in 2002 and 2012. The mediator was DHEA measured in 2001 and 2002. Multilevel path analysis was used to test if males and females differed in violence victimization predicting change in BMI (Model I) and the mediating effect of DHEA change on the above association (Model II). The results of Model I suggested that the change in violence victimization from 1999 to 2000 predicted change in BMI from 2002 to 2012 for females, but not males. Based on Model II, the DHEA change from 2000 to 2001 for females fully mediated the association between violence victimization from 1999 to 2000 and increases in BMI from 2002 to 2012. Our findings suggest that violence victimization in urban areas contributes to the development of obesity among African American female young adults and change in DHEA mediates this link. Violence prevention may have important implications for obesity prevention of African American young women who live in unsafe urban areas. This study also suggests that DHEA may be involved in the violence victimization-obesity link for African American women.

Compassionate and self-image goals as interpersonal maintenance factors in clinical depression and anxiety.

OBJECTIVE: Interpersonal models of depression and anxiety have not examined the role of interpersonal goals in shaping relationships and symptoms. Striving to promote/protect desired self-images (self-image goals) may undermine relationships and increase symptoms, whereas striving to support others (compassionate goals) may be protective, but clinical relevance is unknown. METHOD: We tested effects of compassionate versus self-image goals on interpersonal functioning and symptoms in clinically depressed and/or anxious participants (N = 47) during 10 days of experience sampling, over a 6-week follow-up, and in a dyadic relationship. RESULTS: Participants reported higher conflict and symptoms on days that they most pursued self-image goals, but noted higher perceived support and lower symptoms when pursuing compassionate goals. Goals prospectively predicted symptom changes 6 weeks later. Lastly, informant-rated interpersonal goals predicted relationship satisfaction of both patients and significant others. CONCLUSION: Results suggest the relevance of self-image and compassionate goals for the interpersonal maintenance of depression and anxiety.

Neural circuitry of emotion regulation: Effects of appraisal, attention, and cortisol administration.

Psychosocial well-being requires effective regulation of emotional responding in context of threat or stress. Neuroimaging studies have focused on instructed, volitional regulation (e.g., reappraisal or distancing), largely ignoring implicit regulation that does not involve purposeful effort to alter emotional experience. These implicit processes may or may not involve the same neural pathways as explicit regulatory strategies. We examined the neurobiology of implicit emotional regulation processes and the impact of the stress hormone cortisol on these processes. Our study task employed composite pictures of faces and places to examine neural activity during implicit emotional processing (of emotional faces), while these responses were implicitly regulated by attention shift away from the emotionally evocative stimuli, and while subjects reflectively appraised their own emotional response to them. Subjects completed the task in an fMRI scanner after random assignment to receive placebo or hydrocortisone (HCT), an orally administered version of cortisol. Implicit emotional processing activated insula/IFG, dACC/dMPFC, midbrain and amygdala. With attention shifting, we saw diminished signal in emotion generating/response regions (e.g., amygdala) and increased activations in task specific attention regions like parahippocampus. With appraisal of emotions, we observed robust activations in medial prefrontal areas, where activation is also seen in instructed reappraisal studies. We observed no main effects of HCT administration on brain, but males and females showed opposing neural effects in prefrontal areas. The data suggest that different types of emotion regulation utilize overlapping circuits, but with some strategy specific activation. Further study of the dimorphic sex response to cortisol is needed.

Psychobiology of cumulative trauma: hair cortisol as a risk marker for stress exposure in women.

Childhood trauma (CT) is associated with long-lasting alterations of the hypothalamic-pituitary-adrenal (HPA) axis and elevated risk for stress exposure in adulthood. Although HPA alterations are present in the early aftermath of trauma, it remains unclear how initial HPA activity is associated with subsequent stress exposure and whether CT exposure influences the strength and direction of this association. The present study examined prospective associations between hair cortisol content (HCC) and stress exposure from baseline to 3-month follow-up in young adult women with recent (i.e. past 3 months) exposure to interpersonal violence (IPV; i.e. physical or sexual assault) and non-traumatized controls. History of significant CT abuse or neglect was determined based on clinical cutoffs for a self-report CT measure: 12 women had abuse or neglect and recent IPV exposure (CT + IPV); 7 women had abuse or neglect but no IPV exposure (CT); 15 women had no history of trauma (NTC). HCC was computed for 3 cm sections reflecting cortisol secretion during the 3 months preceding the baseline assessment. The interaction of cumulative trauma and HCC predicted stress exposure over 3-month follow-up, controlling for baseline stress exposure and depressive symptoms. Simple slopes analyses revealed that lower baseline HCC predicted greater stress exposure in the CT + IPV group compared to the CT group; HCC was not associated with stress exposure in the NTC group. The present findings highlight the potential utility of HCC as a predictor of stress exposure for women with a history of childhood abuse or neglect, particularly in the context of recent IPV. Lay summary Adults with a history of CT show long-lasting alterations in major stress response systems, including the HPA axis. They are also more likely to experience stressful life events in adulthood. However, it is not clear how altered HPA activity influences risk for stress exposure and whether CT affects their relationship. The results from this study show that lower HPA activity (measured with hair cortisol) predicted greater stress exposure in women with CT - particularly for women who also experienced recent incidents involving physical or sexual assault.

Mediators of compassionate goal intervention effects on human neuroendocrine responses to the Trier Social Stress Test.

OBJECTIVES: The hypothalamic-pituitary-adrenal (HPA) axis is thought to mediate the effects of stress on illness. Research has identified a limited number of psychological variables that modulate human HPA responses to stressors (e.g. perceived control and social support). Prosocial goals can reduce subjective stress, but have not been carefully examined in experimental settings where pathways of impact on biological stress markers may be traced. Recent work demonstrated that coaching individuals to strive to help others reduced HPA responses to the Trier Social Stress Test (TSST) relative to other cognitive interventions. However, identification of mediational pathways, which were not examined in the original study, is necessary to determine whether the HPA buffering effects were due to helping motivations (compassionate goals; CGs) rather than via previously identified variables such as control or support. METHODS: In this new analysis, we combined the original cortisol data with novel observer ratings of interpersonal behavior and psychological variables during the stress task, and conducted new, theory-driven analyses to determine psychological mediators for the intervention's effect on cortisol responses (N = 54; 21 females, 33 males; 486 cortisol samples). RESULTS: Control, support, and task ego-threat failed to account for the effects of the intervention. As hypothesized, self and observer-rated CGs, as well as observer-rated perceptions of participants' interpersonal behavior as morally desirable (but not as dominant or affiliative) were significant mediators of neuroendocrine responses. CONCLUSIONS: The findings suggest that stress-reduction interventions based on prosocial behavior should target particular motivational and interpersonal features.

PTSD SYMPTOMS ACROSS PREGNANCY AND EARLY POSTPARTUM AMONG WOMEN WITH LIFETIME PTSD DIAGNOSIS.

BACKGROUND: Little is known about trajectories of PTSD symptoms across the peripartum period in women with trauma histories, specifically those who met lifetime PTSD diagnoses prior to pregnancy. The present study seeks to identify factors that influence PTSD symptom load across pregnancy and early postpartum, and study its impact on postpartum adaptation. METHOD: The current study is a secondary analysis on pregnant women with a Lifetime PTSD diagnosis (N = 319) derived from a larger community sample who were interviewed twice across pregnancy (28 and 35 weeks) and again at 6 weeks postpartum, assessing socioeconomic risks, mental health, past and ongoing trauma exposure, and adaptation to postpartum. RESULTS: Using trajectory analysis, first we examined the natural course of PTSD symptoms based on patterns across peripartum, and found four distinct trajectory groups. Second, we explored factors (demographic, historical, and gestational) that shape the PTSD symptom trajectories, and examined the impact of trajectory membership on maternal postpartum adaptation. We found that child abuse history, demographic risk, and lifetime PTSD symptom count increased pregnancy-onset PTSD risk, whereas gestational PTSD symptom trajectory was best predicted by interim trauma and labor anxiety. Women with the greatest PTSD symptom rise during pregnancy were most likely to suffer postpartum depression and reported greatest bonding impairment with their infants at 6 weeks postpartum. CONCLUSIONS: Screening for modifiable risks (interpersonal trauma exposure and labor anxiety) and /or PTSD symptom load during pregnancy appears critical to promote maternal wellbeing.

The Persistence of Experience: Prior Attentional and Emotional State Affects Network Functioning in a Target Detection Task.

Efficient, adaptive behavior relies on the ability to flexibly move between internally focused (IF) and externally focused (EF) attentional states. Despite evidence that IF cognitive processes such as event imagination comprise a significant amount of awake cognition, the consequences of internal absorption on the subsequent recruitment of brain networks during EF tasks are unknown. The present functional magnetic resonance imaging (fMRI) study employed a novel attentional state switching task. Subjects imagined positive and negative events (IF task) or performed a working memory task (EF task) before switching to a target detection (TD) task also requiring attention to external information, allowing for the investigation of neural functioning during external attention based on prior attentional state. There was a robust increase of activity in frontal, parietal, and temporal regions during TD when subjects were previously performing the EF compared with IF task, an effect that was most pronounced following negative IF. Additionally, dorsolateral prefrontal cortex was less negatively coupled with ventromedial prefrontal and posterior cingulate cortices during TD following IF compared with EF. These findings reveal the striking consequences for brain activity following immersion in an IF attentional state, which have strong implications for psychiatric disorders characterized by excessive internal focus.

Impaired contextual modulation of memories in PTSD: an fMRI and psychophysiological study of extinction retention and fear renewal.

Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression.

Presurgical Psychological and Neuroendocrine Predictors of Psychiatric Morbidity After Major Vascular Surgery: A Prospective Longitudinal Study.

OBJECTIVES: Major life stressors, including major surgeries, are often followed by psychiatric symptoms and disorders. Prior retrospective work found abdominal aortic aneurysm (AAA) repair is followed by increased psychiatric morbidity, which may adversely influence physical and functional recovery. Identifying risk factors before surgery, such as dysregulation in stress response systems, might be useful in improving preventative intervention. METHODS: Two hundred sixteen patients receiving open AAA or aortofemoral bypass surgeries, endovascular AAA repair, or nonsurgical AAA treatment were recruited from two vascular surgery services. Psychiatric symptoms and salivary cortisol measures (waking, 4 PM, and 11 PM, before and after low-dose dexamethasone) were obtained at intake and 3- and 9-month follow-ups. RESULTS: After open surgeries, 18% of patients had new psychiatric disorders, compared with 4% of patients receiving endovascular AAA repair or nonsurgical treatment (odds ratio = 6.0, 95% confidence interval = 1.6-22.1, p = .007). Having a history of major depression predicted the onset of new disorders in surgical patients. Presurgical cortisol levels were associated with both baseline (r = 0.23, p < .05) and 9-month (r = 0.32, p < .01) psychiatric symptoms (cortisol B = 1.0, standard error = 0.48, p < .05, in repeated-measures mixed model). CONCLUSIONS: Open AAA repair surgery is prospectively linked to the development of psychiatric morbidity, and history of depression elevates risk. Cortisol measures before surgery are associated with current and future psychological functioning, suggesting potential neurobiological mechanisms that may contribute to vulnerability. These results can help identify surgical patients at risk and point to potential targets for risk reduction interventions.

Longitudinal examination of infant baseline and reactivity cortisol from ages 7 to 16 months.

This study characterized the longitudinal evolution of HPA axis functioning from 7 to 16 months of age and identified individual and environmental factors that shape changes in HPA axis functioning over time. Participants were 167 mother-infant dyads drawn from a larger longitudinal study, recruited based on maternal history of being maltreated during childhood. Salivary cortisol levels were assessed before and after age-appropriate psychosocial stressors when infants were 7 and 16 months old. Maternal observed parenting and maternal reports of infant and environmental characteristics were obtained at 7 months and evaluated as predictors of changes in infant baseline cortisol and reactivity from 7 to 16 months. Results revealed that infants did not show a cortisol response at 7 months, but reactivity to psychosocial stress emerged by 16 months. Individual differences in cortisol baseline and reactivity levels over time were related to infant sex and maternal overcontrolling behaviors, underscoring the malleable and socially informed nature of early HPA axis functioning. Findings can inform prevention and intervention efforts to promote healthy stress regulation during infancy.

Modeling neuroendocrine stress reactivity in salivary cortisol: adjusting for peak latency variability.

In this report, we present growth curve modeling (GCM) with landmark registration as an alternative statistical approach for the analysis of time series cortisol data. This approach addresses an often-ignored but critical source of variability in salivary cortisol analyses: individual and group differences in the time latency of post-stress peak concentrations. It allows for the simultaneous examination of cortisol changes before and after the peak while controlling for timing differences, and thus provides additional information that can help elucidate group differences in the underlying biological processes (e.g., intensity of response, regulatory capacity). We tested whether GCM with landmark registration is more sensitive than traditional statistical approaches (e.g., repeated measures ANOVA--rANOVA) in identifying sex differences in salivary cortisol responses to a psychosocial stressor (Trier Social Stress Test--TSST) in healthy adults (mean age 23). We used plasma ACTH measures as our "standard" and show that the new approach confirms in salivary cortisol the ACTH finding that males had longer peak latencies, higher post-stress peaks but a more intense post-peak decline. This finding would have been missed if only saliva cortisol was available and only more traditional analytic methods were used. This new approach may provide neuroendocrine researchers with a highly sensitive complementary tool to examine the dynamics of the cortisol response in a way that reduces risk of false negative findings when blood samples are not feasible.

Effortful control and context interact in shaping neuroendocrine stress responses during childhood.

Trait and contextual factors can shape individual and group differences in hypothalamic-pituitary-adrenal (HPA) response to stress; but the ways in which these factors may interact with each other to modulate stress activity have rarely been examined. Here, we investigated whether the association between a temperamental self-regulatory trait - Effortful Control (EC) - and HPA axis stress response is moderated by type of laboratory stress in sixty-five children (35 boys). EC was measured at ages 3 and 6 using age-appropriate laboratory batteries as well as mother reports. HPA axis responses were measured at age 7 by randomly assigning children to one of two laboratory stress tasks (frustration vs. fear). Results indicated that EC interacted with stress context in predicting cortisol response. Specifically, lower EC was associated with greater cortisol response (steeper reactivity slopes) in the context of a frustration stressor but this was reversed in a fear context where lower EC was associated with flatter, more gradual activation. It is likely that different components of EC, such as emotion regulation and attention, differentially interact with the stress context. These types of effects and interactions need to be more thoroughly understood in order to meaningfully interpret cortisol reactivity data and better characterize the role of the HPA axis in human psychopathology.

The cortisol awakening response: regulation and functional significance.

In healthy individuals, the majority of cortisol secretion occurs within several hours surrounding morning awakening. A highly studied component of this secretory period is the cortisol awakening response (CAR), the rapid increase in cortisol levels across the first 30-45 min after morning awakening. This strong cortisol burst at the start of the active phase has been proposed to be functional in preparing the organism for the challenges of the upcoming day. Here, we review evidence on key regulatory and functional processes of the CAR and develop an integrative model of its functional role. Specifically, we propose that, in healthy individuals, the CAR is closely regulated by an intricate dual-control system, which draws upon key circadian, environmental and neurocognitive processes to best predict the daily need for cortisol-related action. Fine-tuned CAR expression, in turn, is then assumed to induce potent glucocorticoid action via rapid non-genomic and slower genomic pathways (e.g., affecting circadian clock gene expression) to support and modulate daily activity through relevant metabolic, immunological and neurocognitive systems. We propose that this concerted action is adaptive in mediating two main functions: a primary process to mobilize resources to meet activity-related demands and a secondary process to help the organism counterregulate adverse prior-day emotional experiences.

Changes in Brain Network Connections After Exposure and Response Prevention Therapy for Obsessive-Compulsive Disorder in Adolescents and Adults.

BACKGROUND: Functional alterations of tripartite neural networks during cognitive control (i.e., frontoparietal network [FPN], cingulo-opercular network, and default mode network) occur in patients with obsessive-compulsive disorder (OCD) and may contribute to illness expression. However, the degree to which changes in these networks are elicited by gold standard treatment (e.g., exposure and response prevention [EX/RP]) remains unknown. Understanding how EX/RP modulates network connectivity in adolescent versus adult patients with OCD may aid the identification of developmentally sensitive treatment targets that enhance cognitive control. METHODS: Data from a total of 169 adolescents (13-17 years) and adults (25-40 years; 57% female) were analyzed, including healthy control participants (n = 58) and patients with OCD (n = 111) who were randomized to either EX/RP or an active control therapy (stress management training). Participants performed a flanker task during functional magnetic resonance imaging pre- and posttreatment. To retain sensitivity to individual differences in connectivity, group iterative multiple model estimation was used to assess functional connectivity (i.e., density) within and between brain networks. RESULTS: Significant increases in FPN density and decreases in FPN-default mode network density were observed from pre- to posttreatment in patients who received EX/RP. The opposite patterns of change occurred in patients who received stress management training. These treatment-related changes in network density did not differ across age group. CONCLUSIONS: Results suggest EX/RP-specific changes in task-based connectivity in patients with OCD. Given baseline differences between healthy control participants and patients by age group, these treatment-related changes may indicate restoration of healthy FPN and default mode network development across patients, providing targets for improving response to EX/RP.

Exposure and response prevention versus stress management training for adults and adolescents with obsessive compulsive disorder: A randomized clinical trial.

OBJECTIVE: Though exposure and response prevention (ERP) is a well-proven treatment for OCD across the lifespan, prior RCTs have not studied adolescent and adult patients with the same ERP protocol relative to an active comparator that controls for non-specific effects of treatment. This approach assesses differences in the effect of OCD-specific exposures in affected adolescents and adults and in response to ERP compared to a stress-management control therapy (SMT). METHODS: This assessor-blinded, parallel, 2-arm, randomized, ambulatory clinical superiority trial randomized adolescents (aged 12-18) and adults (24-46) with OCD (N = 126) to 12 weekly sessions of ERP or SMT. OCD severity was measured before, during and after treatment using the child or adult version of the Yale-Brown Obsessive Compulsive Scale (C/Y-BOCS), depending on participant age. We predicted that ERP would produce greater improvement in OCD symptoms than SMT and that there would be no significant post-treatment differences across age groups. RESULTS: ERP (n = 63) produced significantly greater improvements on C/Y-BOCS scores at post-treatment than SMT (n = 63) (Effect size = -0.72, CI = -0.52 to -0.91, p < .001). ERP also produced more treatment responders (ERP = 86%, SMT = 32%; χ2 = 46.37, p < .001) and remitters than SMT (ERP = 39%, SMT = 7%; χ2 = 16.14, p < .001). Finally, there were no statistically significant post-treatment differences in C/Y-BOCS scores between adolescents and adults assigned to ERP. CONCLUSION: A single ERP protocol is superior to SMT in treating both adolescents and adults with OCD. OCD-specific therapy is necessary across the lifespan for optimal outcomes in this highly disabling disorder, though non-specific treatments like SMT are still all-too-commonly provided.

Student mental health outcomes of a clustered SMART for developing an adaptive implementation strategy to support school-based CBT delivery.

PURPOSE: Most youth experiencing anxiety/depression lack access to evidence-based mental health practices (EBPs). School-delivered care improves access, and various support can help school professionals (SPs; school social workers, counselors) deliver EBPs, like Cognitive Behavioral Therapy (CBT). Understanding implementation strategies' impact on downstream mental health outcomes is crucial to scaling up EBPs to address the treatment gap, but it has rarely been assessed. METHODS: This paper compares implementation strategies' impact on change in student outcomes, collected as exploratory outcomes from a type III hybrid implementation-effectiveness trial. A clustered, sequential, multiple-assignment randomized trial design was used, which embedded four implementation supports that differentially sequence three implementation strategies, Replicating Effective Programs (REP), Coaching, and Facilitation. Prior to the first randomization, N = 169 SPs from 94 Michigan high schools each identified up to 10 students whom they believed could benefit from CBT and facilitated student survey completion. Changes in students' depression (Patient Health Questionnaire-9, modified for teens) and anxiety symptoms (Generalized Anxiety Disorder-7) over 10 months were compared across the four sequences of implementation support using a generalization of a marginal, weighted least squares approach developed for a clustered SMARTs. RESULTS: Small, non-clinically significant reductions in symptoms over the study period were found. Pairwise comparisons found no significant differences in symptom change across the four implementation strategies. The difference in the estimated mean PHQ-9T/GAD-7 scores between the least and the most intensive strategies (REP vs. REP+Coaching+Facilitation) was 1.04 (95%CI = -0.95, 3.04) for depression and 0.82 (95%CI = -0.89, 2.52) for anxiety. DISCUSSION: No difference in symptom change was found across the four implementation strategies. Multiple forms of implementation support may be useful for improving student mental health outcomes. TRIAL REGISTRATION: NCT03541317-Registered on 29 May 2018 on ClinicalTrials.gov PRS.

Subjective uncertainty and limbic hyperactivation in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is often associated with pathological uncertainty regarding whether an action has been performed correctly or whether a bad outcome will occur, leading to compulsive "evidence gathering" behaviors aimed at reducing uncertainty. The current study used event-related functional magnetic resonance imaging to investigate neural functioning in OCD patients and controls as subjective certainty was rated in response to sequential pieces of evidence for a decision. Uncertainty was experimentally manipulated so that some decisions were associated with no "objective" uncertainty (all observed evidence pointed to one correct choice), whereas other decisions contained calculable but varying levels of objective uncertainty based on displayed probabilities. Results indicated that OCD patients differed from controls on decisions that contained no objective uncertainty, such that patients rated themselves as more uncertain. Patients also showed greater activation in a network of brain regions previously associated with internally-focused thought and valuation including ventromedial prefrontal cortex, parahippocampus, middle temporal cortex, as well as amygdala and orbitofrontal cortex/ventral anterior insula. In the patient group, a significantly greater number of positive intersubject correlations were found among several of these brain regions, suggesting that this network is more interconnected in patients. OCD patients did not differ from controls on decisions where task parameters led to uncertainty. These results indicate that OCD is associated with hyperactivation in a network of limbic/paralimbic brain regions when making decisions, which may contribute to the greater subjective experience of doubt that characterizes the disorder.