Alterations in BNST Intrinsic Functional Connectivity in Early Abstinence from Alcohol Use Disorder.

AIMS: Maintaining abstinence from alcohol use disorder (AUD) is extremely challenging, partially due to increased symptoms of anxiety and stress that trigger relapse. Rodent models of AUD have identified that the bed nucleus of the stria terminalis (BNST) contributes to symptoms of anxiety-like behavior and drug-seeking during abstinence. In humans, however, the BNST's role in abstinence remains poorly understood. The aims of this study were to assess BNST network intrinsic functional connectivity in individuals during abstinence from AUD compared to healthy controls and examine associations between BNST intrinsic functional connectivity, anxiety and alcohol use severity during abstinence. METHODS: The study included resting state fMRI scans from participants aged 21-40 years: 20 participants with AUD in abstinence and 20 healthy controls. Analyses were restricted to five pre-selected brain regions with known BNST structural connections. Linear mixed models were used to test for group differences, with sex as a fixed factor given previously shown sex differences. RESULTS: BNST-hypothalamus intrinsic connectivity was lower in the abstinent group relative to the control group. There were also pronounced sex differences in both the group and individual analyses; many of the findings were specific to men. Within the abstinent group, anxiety was positively associated with BNST-amygdala and BNST-hypothalamus connectivity, and men, not women, showed a negative relationship between alcohol use severity and BNST-hypothalamus connectivity. CONCLUSIONS: Understanding differences in connectivity during abstinence may help explain the clinically observed anxiety and depression symptoms during abstinence and may inform the development of individualized treatments.

Alterations in connectivity of the bed nucleus of the stria terminalis during early abstinence in individuals with alcohol use disorder.

BACKGROUND: For individuals with Alcohol Use Disorder (AUD), long-term recovery is difficult in part due to symptoms of anxiety that occur during early abstinence and can trigger relapse. Research in rodent models of AUD has identified the bed nucleus of the stria terminalis (BNST), a small, sexually dimorphic, subcortical region, as critical for regulating anxiety-like behaviors during abstinence, particularly in female mice. Furthermore, prolonged alcohol use and subsequent abstinence alter BNST afferent and efferent connections to other brain regions. To our knowledge, however, no studies of early abstinence have investigated BNST structural connectivity in humans during abstinence; this study addresses that gap. METHODS: Nineteen participants with AUD currently in early abstinence and 20 healthy controls completed a diffusion tensor imaging (DTI) scan. BNST structural connectivity was evaluated using probabilistic tractography. A linear mixed model was used to test between-groups differences in BNST network connectivity. Exploratory analyses were conducted to test for correlations between BNST connectivity and alcohol use severity and anxiety within the abstinence group. Sex was included as a factor for all analyses. RESULTS: The BNST showed stronger structural connectivity with the BNST network in early abstinence women than in control women, which was not seen in men. Women also showed region-specific differences, with stronger BNST-hypothalamus structural connectivity but weaker vmPFC-BNST structural connectivity than men. Exploratory analyses also demonstrated a relationship between alcohol use severity and vmPFC-BNST structural connectivity that was moderated by sex. CONCLUSIONS: This study is the first to demonstrate BNST structural connectivity differences in early abstinence and revealed key sex differences. The sex-specific differences in BNST structural connectivity during early abstinence could underlie known sex differences in abstinence symptoms and relapse risk and help to inform potential sex-specific treatments.

Anxiety during abstinence from alcohol: A systematic review of rodent and human evidence for the anterior insula's role in the abstinence network.

Alcohol Use Disorder (AUD) is a chronic, relapsing disease that impacts almost a third of Americans. Despite effective treatments for attaining sobriety, the majority of patients relapse within a year, making relapse a substantial barrier to long-term treatment success. A major factor contributing to relapse is heightened negative affect that results from the combination of abstinence-related increases in stress-reactivity and decreases in reward sensitivity. Substantial research has contributed to the understanding of reward-related changes in AUD. However, less is known about anxiety during abstinence, a critical component of understanding addiction as anxiety during abstinence can trigger relapse. Most of what we know about abstinence-related negative affect comes from rodent studies which have identified key brain regions responsible for abstinence-related behaviors. This abstinence network is composed of brain regions that make up the extended amygdala: the nucleus accumbens (NAcc), the central nucleus of the amygdala (CeA), and the bed nucleus of the stria terminalis (BNST). More recently, emerging evidence from rodent and human studies suggests a fourth brain region, the anterior insula, might be part of the abstinence network. Here, we review current rodent and human literature on the extended amygdala's role in alcohol abstinence and anxiety, present evidence for the anterior insula's role in the abstinence network, and provide future directions for research to further elucidate the neural underpinnings of abstinence in humans. A better understanding of the abstinence network is critical toward understanding and possibly preventing relapse in AUD.

Bed nucleus of the stria terminalis and amygdala responses to unpredictable threat in children.

Substantial evidence from studies in humans suggests the amygdala is pivotal for anxiety. Findings from animal models and translational studies suggests the bed nucleus of the stria terminalis (BNST) is also critical for anxiety and the anticipation of unpredictable threat in adults. However, it remains unknown whether the BNST is involved in unpredictable threat anticipation in children. Forty-two 8-10-year-olds completed resting-state functional magnetic resonance imaging (fMRI) scans and an unpredictable threat fMRI task in which they were trained to associate cues with images. Intrinsic connectivity analyses were performed to establish functional BNST and amygdala networks. BNST and amygdala activation to cues and images was tested. Significant findings were followed by task-based functional connectivity analyses. Children showed evidence for BNST and amygdala intrinsic connectivity that was similar to previous patterns observed in adults. In response to unpredictable cues relative to neutral face cues, children had a significant amygdala response but no response in the BNST. The amygdala, but not the BNST, also showed a significantly greater response to fear face images relative to neutral images. Thus, unpredictable threat activated the amygdala, but not BNST, in children. This finding is contrary to studies showing robust BNST activation to unpredictable threat in adults and may suggest that the BNST's role in threat processing emerges later in development.

Social anxiety is associated with BNST response to unpredictability.

BACKGROUND: Anxiety disorders are highly prevalent and cause substantial suffering and impairment. Whereas the amygdala has well-established contributions to anxiety, evidence from rodent and nonhuman primate models suggests that the bed nucleus of the stria terminalis (BNST) may play a critical, and possibly distinct, role in human anxiety disorders. The BNST mediates hypervigilance and anticipatory anxiety in response to an unpredictable or ambiguous threat, core symptoms of social anxiety, yet little is known about the BNST's role in social anxiety. METHODS: Functional magnetic resonance imaging was used to measure neural responses during a cued anticipation task with an unpredictable, predictable threat, and predictable neutral cues followed by threat or neutral images. Social anxiety was examined using a dimensional approach (N = 44 adults). RESULTS: For unpredictable cues, higher social anxiety was associated with lower BNST-amygdala connectivity. For unpredictable images, higher social anxiety was associated with greater connectivity between the BNST and both the ventromedial prefrontal cortex and the posterior cingulate cortex and lower connectivity between the BNST and postcentral gyrus. Social anxiety moderated the BNST-amygdala dissociation for unpredictable images; higher social anxiety was associated with BNST > amygdala response to unpredictable threat relative to unpredictable neutral images. CONCLUSIONS: Social anxiety was associated with alterations in BNST responses to unpredictability, particularly in the BNST's interactions with other brain regions, including the amygdala and prefrontal cortex. To our knowledge, these findings provide the first evidence for the BNST's role in social anxiety, which may be a potential new target for prevention and intervention.

Neurocircuitry underlying risk and resilience to social anxiety disorder.

BACKGROUND: Almost half of children with an inhibited temperament will develop social anxiety disorder by late adolescence. Importantly, this means that half of children with an inhibited temperament will not develop social anxiety disorder. Studying adults with an inhibited temperament provides a unique opportunity to identify neural signatures of both risk and resilience to social anxiety disorder. METHODS: Functional magnetic resonance imaging (fMRI) was used to measure brain activation during the anticipation of viewing fear faces in 34 young adults (17 inhibited, 17 uninhibited). To identify neural signatures of risk, we tested for group differences in functional activation and connectivity in regions implicated in social anxiety disorder, including the prefrontal cortex, amygdala, and insula. To identify neural signatures of resilience, we tested for correlations between brain activation and both emotion regulation and social anxiety scores. RESULTS: Inhibited subjects had greater activation of a prefrontal network when anticipating viewing fear faces, relative to uninhibited subjects. No group differences were identified in the amygdala. Inhibited subjects had more negative connectivity between the rostral anterior cingulate cortex (ACC) and the bilateral amygdala. Within the inhibited group, those with fewer social anxiety symptoms and better emotion regulation skills had greater ACC activation and greater functional connectivity between the ACC and amygdala. CONCLUSIONS: These findings suggest that engaging regulatory prefrontal regions during anticipation may be a protective factor, or putative neural marker of resilience, in high-risk individuals. Cognitive training targeting prefrontal cortex function may provide protection against anxiety, especially in high-risk individuals, such as those with inhibited temperament.

Characterizing Adolescent Disclosures of Suicidal Thoughts and Behavior to Parents.

PURPOSE: Suicidal ideation and suicidal behavior (SI/SB) are prevalent among adolescents. Treatment of SI/SB in adolescents relies on their disclosure, yet there is limited research on adolescent SI/SB disclosure experiences. Understanding who they disclose to and how they experience their parents' responses to their disclosures is important, as parents are often involved in adolescent mental health treatment. METHODS: The present study characterized adolescent SI/SB disclosures in a sample of psychiatrically hospitalized adolescents, examining to whom they disclosed SI/SB, perceived parental responses to SI/SB disclosures, and what they would prefer their parents did differently in response to SI/SB disclosures. RESULTS: Results indicate that over 50% of youth disclosed their SI/SB directly to their parent and approximately 15%-20% of youth did not disclose their SI/SB to anyone prior to psychiatric hospitalization. Perceived parental responses to disclosures varied, including both validating and invalidating responses. DISCUSSION: Findings have important implications for supporting parents and adolescents in discussing SI/SB.

Self-injurious thoughts and behaviors and alterations in positive valence systems: A systematic review of the literature.

Self-injurious thoughts and behaviors (SITBs), which include suicidal ideation (SI), suicide attempts (SA), and nonsuicidal self-injury (NSSI), are prevalent and associated with impairments in functioning and elevated risk of suicide deaths. Preventing suicide is a complex problem, with numerous systems likely contributing to the onset and maintenance of SITBs, and there is a critical need to identify more precise predictors of risk. Positive valence systems (PVS) are an understudied domain with promise for improving understanding of risk processes underlying SITBs. In this systematic review, we evaluate the evidence for the potential role of altered PVS function in SI, SA, and/or NSSI, including alterations in reward responsiveness, learning, and valuation assessed through behavioral, physiological and circuit measures. Results provide preliminary support for associations between distinct aspects of PVS function and alterations in SITBs. Specifically, SI appears to be characterized by low reward responsiveness, whereas little research has examined reward responsiveness in SA, and NSSI has been characterized by hyper-responsiveness to rewards. Alterations in reward learning and valuation are commonly examined in SA, with some evidence that they may be more strongly associated with attempts than SI or NSSI. At the same time, the literature is limited in that some constructs are commonly examined in one form of SITBs but not others. Further, research is predominantly cross-sectional and focused on adults, raising questions about the role of PVS function in developmental pathways to SITBs. We conclude by integrating the research to date and highlighting promising directions for future research.

Measurement-Based Care in the Adolescent Partial Hospital Setting: Implementation, Challenges, & Future Directions.

In this paper, we describe the process of implementing measurement-based care (MBC) in the adolescent partial hospital program setting. First, we outline the rationale for incorporating MBC in this treatment setting. Second, we describe the partial hospital setting in which implementation took place, including the patient population, treatment providers, and structure of programming. Next, we outline the initial implementation of standardized assessments into our programming, including key initial considerations and challenges during implementation. We describe the importance of considering the primary symptom presentations of the patient population when selecting assessment tools, the importance of leveraging existing electronic health record tools to efficiently track and record data collection, and the ability to integrate assessments into clinical workflows. Fourth, we present data describing compliance with implementation, patient outcomes, and providers' attitudes towards and knowledge of MBC following implementation. We found after the initial implementation period, compliance was high. We also found providers had an overall positive perception of the use of MBC, reporting they perceived it to be helpful to both their clinical practice and patient outcomes. Finally, we discuss future directions for best utilizing standardized assessments in intensive treatment settings.

Longitudinal predictors of depression, anxiety, and alcohol use following COVID-19-related stress.

The COVID-19 pandemic imposed profound effects on health and daily life, with widespread stress exposure and increases in psychiatric symptoms. Despite these challenges, pandemic research provides unique insights into individual differences in emotion and cognition that predict responses to stress, with general implications for understanding stress vulnerability. We examined predictors of responses to COVID-19-related stress in an online sample of 450 emerging adults recruited in May 2020 to complete questionnaires assessing baseline stress and psychiatric symptoms, rumination, cognitive reappraisal use and intolerance of uncertainty. Stress and symptoms were re-assessed 3 months later (N = 200). Greater pandemic-related stressful events were associated with increases in symptoms of depression, anxiety and alcohol use severity. Additionally, individual differences in emotional and cognitive styles emerged as longitudinal predictors of stress responses. Specifically, greater rumination predicted increased depression. Reduced cognitive reappraisal use interacted with stress to predict increases in alcohol use. An unexpected pattern emerged for intolerance of uncertainty, such that stress was associated with increases in depression for those high in intolerance of uncertainty but increases in alcohol use at relatively low levels of intolerance of uncertainty. These results highlight unique vulnerabilities that predict specific outcomes following stress exposure and offer potential prevention targets.

Co-occurring psychiatric symptoms are associated with increased psychological, social, and medical impairment in opioid dependent pregnant women.

The interaction of psychiatric symptoms with drug dependence during pregnancy is not well understood. This study examines the relationship of psychiatric symptoms to severity of drug use and drug-related problems among participants in a clinical trial of pharmacologic treatment of opioid dependence during pregnancy (N = 174). A total of 64.6% reported additional psychiatric symptoms (48.6% mood symptoms, 40.0% anxiety symptoms, and 12.6% suicidal thinking). Women who endorsed co-occurring psychiatric symptoms showed more severe impairment on the Addiction Severity Index. Further investigation is warranted to understand the effect of psychiatric symptoms on long-term maternal and neonatal outcomes.

Treatment of Alcohol Intoxication at University Health Services: Examining Clinical Characteristics, Drinking Patterns, and Adherence with Referral.

OBJECTIVE: This study examines demographics, clinical characteristics, and drinking patterns of students presenting with alcohol intoxication at a university health service. PARTICIPANTS: The sample included one hundred students (50% female, 48% freshmen) treated for alcohol intoxication at university student health services. Complete medical charts were obtained for 80 students (43% female, 46% freshmen). METHODS: A prospective case review was performed between September 2005 and March 2006. RESULTS: Although males reported having more drinks before admission, drinking more frequently, and having more drinks per drinking day than females, there were no other gender differences. Freshmen comprised almost half the admissions, but there were no significant differences in drinking patterns across school years. While only 54% of students were given follow-up referrals, 72.2% of students complied with recommended referrals. Additional assessment information included alcohol use disorders sceening scores, history of previous alcohol intoxication and problems related to use, symptoms of anxiety and depression, and use of anti-depressant medication. CONCLUSIONS: These results suggest that further investigations of student characteristics and experiences prior to contact with university health services are warranted and may necessary to the development and implementation of programs to reduce harmful alcohol consumption.

Electroconvulsive Therapy as a Safe, Effective Treatment for Catatonia in an Adolescent with a Nasogastric Tube: A Case Report.

This case provides support for electroconvulsive therapy as a safe treatment in adolescents with a feeding tube. The patient presented to our hospital with symptoms of catatonia with minimal oral intake. She had stopped eating, had minimal interaction with her environment, and spent weeks with a nasogastric tube for nutritional support. She had been referred for electroconvulsive therapy but was unable to find a local provider who would perform it on an adolescent with a nasogastric tube. She came to our hospital and received 9 rounds of electroconvulsive therapy with improvement of her catatonia and no aspiration or adverse events.

Meeting Youth Where They Are: Substance Use Disorder Treatment in Schools.

Providing school-based mental health treatment offers an opportunity to reach a greater number of affected youth by providing services in the setting where youth spend the majority of their time. In some contexts, even a single session of assessment has been linked with significant decreases in substance use; however, more robust treatments are likely needed to sustain these decreases over time. Empirically based individual and group treatments designed for delivery in clinic settings can readily be adapted for implementation in school settings. School-based delivery of substance use services offers an important opportunity to bridge a significant gap in services.

Altered Prefrontal Cortex Function Marks Heightened Anxiety Risk in Children.

OBJECTIVE: Anxiety disorders are prevalent and cause substantial disability. An important risk factor for anxiety disorders is inhibited temperament, the tendency to be shy and to avoid new situations. Inhibited adults have heightened amygdala activation and less flexible engagement of the prefrontal cortex (PFC); however, it remains unknown whether these brain alterations are present in inhibited children before the onset of anxiety disorders. METHOD: A total of 37 children (18 inhibited and 19 uninhibited), 8 to 10 years of age, completed a task testing anticipation and viewing of threat stimuli and social stimuli in the magnetic resonance imaging (MRI) scanner. Brain activation and functional connectivity were measured. RESULTS: During the anticipation of threat stimuli, inhibited children failed to show the robust PFC engagement observed in the uninhibited children. In contrast, when viewing social stimuli, inhibited children had increased medial PFC and dorsolateral PFC activation. Connectivity analyses revealed a pattern of reduced connectivity between prefrontal and limbic regions and among distinct PFC regions in the inhibited group. The medial PFC emerged as a key hub of the altered PFC circuitry in inhibited children. CONCLUSION: This study provides new evidence of a neural signature of vulnerability to anxiety disorders. By investigating both anticipation and response to images, we identified that high-risk, inhibited children have widespread alterations in PFC function and connectivity, characterized by an inability to proactively prepare for social threat combined with heightened reactivity to social stimuli. Thus, children at high risk for anxiety show significantly altered prefrontal cortical function and connectivity before the onset of anxiety disorders.

Disgust proneness and associated neural substrates in obesity.

Defects in experiencing disgust may contribute to obesity by allowing for the overconsumption of food. However, the relationship of disgust proneness and its associated neural locus has yet to be explored in the context of obesity. Thirty-three participants (17 obese, 16 lean) completed the Disgust Propensity and Sensitivity Scale-Revised and a functional magnetic resonance imaging paradigm where images from 4 categories (food, contaminates, contaminated food or fixation) were randomly presented. Independent two-sample t-tests revealed significantly lower levels of Disgust Sensitivity for the obese group (mean score = 14.7) compared with the lean group (mean score = 17.6, P = 0.026). The obese group had less activation in the right insula than the lean group when viewing contaminated food images. Multiple regression with interaction analysis revealed one left insula region where the association of Disgust Sensitivity scores with activation differed by group when viewing contaminated food images. These interaction effects were driven by the negative correlation of Disgust Sensitivity scores with beta values extracted from the left insula in the obese group (r = -0.59) compared with a positive correlation in the lean group (r = 0.65). Given these body mass index-dependent differences in Disgust Sensitivity and neural responsiveness to disgusting food images, it is likely that altered Disgust Sensitivity may contribute to obesity.

The role of schools in substance use prevention and intervention.

Schools provide an ideal setting for screening, brief interventions, and outpatient treatment for substance use disorders (SUD). Individual treatment for SUD is effective at decreasing substance use as well as substance-related harm. In some contexts, rather than being helpful, group interventions can result in harm to participants; therefore, individual treatment may be preferred. Early interventions for adolescents who are using alcohol and other drugs (AOD) are generally effective in decreasing frequency and quantity of AOD use as well as decreasing risky behaviors.

Educational impacts of the social and emotional brain.

Advances in neuroscience related to social and emotional development have significant implications for educational practice. The human brain cannot fully dissociate cognitive from emotional events, and therefore educational programming that recognizes the importance of social-emotional development also facilitates academic achievement. The ideal learning environment encourages the development of social-emotional and academic neuronal pathways. Taking advantage of the emerging understanding of the developing brain offers opportunities to facilitate greater academic gains.

Implementing clinical outcomes assessment in everyday school mental health practice.

Evidence-based assessment (EBA) has been shown to improve clinical outcomes, but this practice is frequently not implemented in school mental health practice. This article reviews potential barriers to implementation and offers practical strategies for addressing these challenges. Several valid and reliable tools for assessment are reviewed, and information is provided on clinical use. Case examples of EBA implementation in school mental health settings are provided to illustrate how these tools can be used in everyday practice by school mental health clinicians.

Being present at school: implementing mindfulness in schools.

Developmentally sensitive efforts to help students learn, practice, and regularly use mindfulness tactics easily and readily in and beyond the classroom are important to help them manage future stresses. Mindfulness emphasizes consciously focusing the mind in the present moment, purposefully, without judgment or attachment. Meditation extends this to setting aside time and places to practice mindfulness, and additionally, yoga includes physical postures and breathing techniques that enhance mindfulness and meditation. Several mindfulness programs and techniques have been applied in schools, with positive benefits reported. Some elements of these programs require modifications to be sensitive to the developmental state of the children receiving mindfulness training.