Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most common psychiatric disorders affecting adolescents. Treatment often focuses on managing symptoms, including distractibility, poor concentration, disorganization, hyperactivity, and impulsivity. A successful transition to adulthood requires interpersonal, organizational, and planning skills, making adolescence a critical time to treat ADHD symptoms. Sibley et al. (2014) reviewed treatment literature on ADHD in adolescents and concluded that medication and behavior therapy both produce similar effects on ADHD symptoms in adolescents. This project aims to update the results of the prior review using the past ten years of research. First, an electronic database search was conducted using four categories of terms: (1) sample age, (2) disorder, (3) treatment, and (4) randomized control trial. Experts were also contacted to request additional articles published during the designated period. Inclusion criteria were then applied: (1) published between 2013-present, (2) ages 10-19, (3) ADHD diagnosis, (4) quantitative data reported for at least one ecologically valid outcome measure (e.g., ADHD symptom severity), (5) in studies where individuals not meeting age or diagnostic criteria are included, data for adolescents with ADHD must be presented separately, (6) must evaluate treatment efficacy. 20% of the studies were also randomly selected for an inter-rater reliability probe. Next, data were collected based on the type of study, methodology, and participant demographics for every included study. Effect sizes were also calculated for several outcome measures. This review is still in its preliminary stages but will provide an updated review of the most effective pharmacological and non-pharmacological treatments for ADHD in adolescents. It will demonstrate the considerable growth in the number and highlight the effectiveness of available treatments. The next step will include quantifying data to determine trends for each treatment and conclude the review by summarizing our findings.

 Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that often results in deficits in communication, social skills, and emotion regulation. Additional concerns include disruptions to the sleep wake cycle that results from circadian rhythm dysfunction. 40% of individuals with ASD also have clinically significant anxiety, which tends to exacerbate pre-existing behavioral issues and social deficits. Previous studies suggest an association between increased sleep dysfunction and increased issues with anxiety in typically developing (TD) adults, and have insinuated a possible bidirectional relationship between the two. This study aims to look at the relationship between sleep quality and anxiety in adults with and without ASD. 89 adults (ASD=39) from a longitudinal five-site NIH-funded study on sex differences in autism were included. Participants completed the Munich Chronotype Questionnaire (MCTQ), a measure of the amount of sleep, based on sleep-wake times, and the Screen for Adult/Child Anxiety Related Disorders for a measure of generalized anxiety. Analysis will include (1) independent sample t-tests to examine group differences in anxiety and sleep duration and (2) correlations between sleep duration (MCTQ) and generalized anxiety subscore from the SCAARED measure for the group with ASD and the typically developing group. I hypothesize that individuals with ASD compared to TD will demonstrate higher anxiety scores and worse sleep quality. I also hypothesize that there will be a correlation between higher anxiety scores and shorter sleep duration. Additionally we will explore sex differences in anxiety and sleep. If sleep quality is related to anxiety, this might support the increased use of sleep behavioral interventions to improve mental health in individuals with autism spectrum disorders.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is characterized by difficulties in social communication skills, and repetitive restricted behaviors. ASD has been associated with alexithymia, or difficulties processing one’s and/or own emotions. Prior research suggests, individuals with alexithymia are at increased risk of developing disordered eating patterns, particularly if they are male (Shank, 2019; Larsen, 2006). Disordered eating tends to be associated with other psychopathology and possible to be comorbid with ASD. Individuals with ASD are also at increased risk of developing disordered eating (Huke, 2013), however it is unknown if the relationship between alexithymia and disordered eating is also found in autistic individuals. Thus, the aim of this study is to investigate sex differences in alexithymia and disordered eating patterns in individuals with and without ASD. 108 adults (ASD n=58, Male n=35) were included; all participants had an IQ ≥70. Alexithymia was measured using the Toronto Alexithymia Scale which is a 20-item instrument describing feelings, identifying feelings, and externally oriented thinking. Scores ≥61 indicate alexithymia . Eating behavior was measured using the Adult Behavior Eating Questionnaire which is a 35-item instrument involving 8 subscales including hunger, food responsiveness, emotional overeating, enjoyment of food, satiety responsiveness, emotional undereating, food fussiness, and slowness in eating. We expect to see a correlation between alexithymia and eating behavior in the autistic group, similar to what has been previously found in non-autistic groups. We also hypothesize that this correlation will be present for autistic males but not autistic females. This study will contribute to better understanding if alexithymia and eating behavior patterns are found in individuals with ASD, and whether or not sex mediates this relationship. If this relationship were true, this may affect how interventions for ASD are administered and label alexithymia as a risk factor for disordered eating.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social communicative impairments and sensory sensitivities. Additionally, the physical and social changes that occur with puberty may be a turbulent time for adolescents. Earlier pubertal timing has been correlated with higher internalizing mental health symptoms for neurotypical girls with earlier onset of menarche in females being tied with higher rates of depression that persists into adulthood. This study investigates the relation between pubertal timing and internalizing mental health problems for autistic and non-autistic female adolescents in a longitudinal study. 23 female ASD participants (ages 8 to 17) and 42 female neurotypical participants (ages 8 to 17) from a NIH-funded project investigating sex and gender differences in individuals with autism are included. Participant data was collected at a second timepoint, 3 to 8 years later. Data on pubertal development was collected using the Pubertal Development Scale, a parent or self-report measure of physical development. Depression and anxiety were assessed using the Child Behavior Check List, a parent-report behavioral checklist of mental health symptoms at the first time point, and a self-report version of the CBCL at the second time point. First, we examine pubertal timing variation by calculating residuals of a pubertal maturation by time regression plot. Second, we will investigate the relationship between puberty timing and depression and anxiety using a correlation test. To further analyze this relationship between pubertal timing predicting future depression and anxiety, we will run a multiple regression test. I predict that the relationship between pubertal timing and depression and anxiety will be greater for autistic girls than for neurotypical girls. This study’s data can add a neurodiverse perspective on how pubertal timing impacts mental health in females and could provide evidence for the need of interventions and additional support to adolescent females with ASD.

Building strong relationships between parents and teachers is critical to supporting young children in developing key social, emotional, and pre-academic skills. Especially in preschool, parent-teacher relationships can support a young child’s development across home and school. Communication is an important aspect of successful parent-teacher relationships; however parents and teachers face interpersonal, intrapersonal, and structural barriers to communicating with one another. This study aims to elevate the voices of racial and ethnic minoritized parents of a preschooler and preschool teachers to understand barriers to communicating and strategies to overcome these barriers. Using a qualitative approach, we conducted semi-structured interviews with 9 parents of a preschool child and 7 preschool teachers at two local early childhood centers. Using a codebook, I am currently analyzing all interviews to answer the following research questions: 1) What type of communication do parents and teachers want? 2) What barriers do parents and teachers face when communicating? and 3) What are some strategies for improving communication between parents and teachers? Preliminary results indicate that both parents and teachers desire open, honest communication. Parents expressed wanting daily communication related to how their child was doing in school. Teachers expressed a desire for parents to understand more about their kids and to be able to speak to parents when they have a concern about their child’s behavior. Despite a desire for communication, both parents and teachers describe feeling unsatisfied by their current level of communication, citing how COVID-19 has limited their ability to communicate. Some strategies discussed included increasing face-to-face contact, having more events at school, and creative ways for daily communication (e.g., interactive platform, daily notes, etc.). Through listening to parents and preschool teachers about their current experiences, we hope to identify ways to improve communication between parents and teachers, ultimately improving young children’s outcomes.

Autism Spectrum Disorders (ASD) refer to neurodevelopmental difficulties in communication and social interaction. It is thought that 94% of autistic adults have used camouflaging behaviors at some point in their lives, meaning that they have developed certain behaviors to blend in the social world and to “hide” their autistic differences. Camouflaging behaviors include: masking - hiding the autistic features; compensation - practicing certain behaviors to compensate for certain social shortcomings; and assimilation - trying to fit in so they are not singled out (Hull et al., 2018). We are interested in the relationship between camouflaging behaviors and social communication in individuals with and without autism. Data from 85 participants (42 ASD, 48 females) ranging from 15 to 23 years old from the NIH funded study on sex and differences in autism were included in the analysis. Autism diagnosis was confirmed via standardized tests and all participants had an IQ of 70 or higher. Participants completed the Camouflaging Autistic Traits Questionnaire (CAT-Q), a 25-item questionnaire that tests the degree of using camouflaging strategies, and Vineland Adaptive Behavior Scales, a parental interview that informs the diagnosis of intellectual and developmental disabilities. We predict significantly higher camouflaging behaviors and lower socialization skills in the autistic group compared to the non-autistic group. We predict a positive correlation between CAT-Q scores and Vineland socialization scores in the autistic group, since by resembling their peers will make their parents report better social skills. We also predict that the correlation between masking and social skills will be higher in females than males in both groups, as females are found to have higher social motivations (Cook, Ogden, & Winstone, 2018). Camouflaging may prevent others from recognizing the symptoms of autism and fail to get diagnosis. Therefore, it is important to detect camouflaging behaviors so autistic children get timely treatments.

Parent-teacher relationships are important in supporting young children’s social and emotional development. Especially in preschool, strong parent-teacher relationships can support a preschooler’s development across home and school. Despite the importance of parent-teacher relationships, parents from racial and ethnic minority backgrounds report having lower-quality relationships with their child’s preschool teacher. In this qualitative study, we sought to evaluate the voices of parents from racial and ethnic minority backgrounds, to understand barriers to and strategies for creating strong parent-teacher relationships. As part of a community-based partnership, we partnered with local preschools that serve a majority of underrepresented students. I assisted in conducting interviews with nine parents, in which three identified as Asian, one identified as Black/African American, three identified as white, and two identified as more than one race. During the interviews we asked parents questions about barriers at the individual, center, and systematic level that stand in the way of establishing close relationships with their child’s teacher, as well as potential solutions. My team is currently in the process of coding and analyzing all transcripts to explore barriers and solutions in more detail. Preliminary results reveal that parents brought up several barriers including time, limited face to face interaction, lack of communication, and feeling unwelcome in their child’s school. These barriers were described as impediments to the parent’s ability to form relationships with their child’s preschool teachers. We are currently analyzing and working with our community partners to identify solutions to improving parent-teacher relationships. The findings of this study are important in understanding how to support parents from racial and ethnic minority backgrounds in forming and maintaining strong relationships with their child’s preschool teacher.

Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits in social communication and interactions, and repetitive behaviors or interests. Children with ASD are more likely to show food selectivity than neurotypical (NT) children, and their restricted food consumption may be associated with nutritional deficiencies. Eating disorders are serious mental health conditions that can have long term health-related consequences. Understanding behavior surrounding eating habits is paramount to developing treatments that are effective for children with autism. In youth without autism, self-compassion impacts eating behaviors. Higher self-compassion is causally linked to lower eating pathology. This study aims to extend this work to examine whether self-compassion influences eating behaviors in adolescents with ASD. Participants included children with ASD (n = 37) and children with NT development (n = 52) between the ages of 13 - 17 years. Parents of participants completed the Child Eating Behavior Questionnaire, and participants completed the Self-Compassion Inventory for Youth survey. We compared emotional overeating and emotional under eating to the self-compassionate coping scale and self-punitive coping scale. Given the stereotyped and repetitive behaviors of adolescents with ASD, we expect a similar relationship between self-compassion and eating behavior seen in studies with neurotypical individuals, to also exist within an ASD group. Specifically, we hypothesize: (1) a positive correlation between emotional overeating and self-punitive coping, (2) a positive correlation between emotional under eating and self-punitive coping, (3) a negative correlation between emotional overeating and the self-compassionate coping scale, and (4) a negative correlation between emotional under eating and the self-compassionate coping scale. This study will offer more insight into the role of self-compassion and eating behavior of ASD adolescents. If the hypothesized correlations exist within the ASD and NT groups, we can look for similar risk factors of disordered eating behavior within ASD adolescents.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by differences in social interaction and communication, as well as repetitive behaviors (APA 2013). Per Kanne and Mazurek (2011), 56% of 1380 children and adolescents diagnosed with ASD engaged in some form of aggression towards family, teachers, or peers. Aggressive behaviors can prevent youth with ASD from being able to engage in learning opportunities and community events. An important factor in decreasing rates and severity of aggression is through the identification of social and environmental factors that may impact the stability of aggressive behaviors. The aim of this study is to look at factors that may impact the stability of aggressive behaviors in a longitudinal sample of autistic and non-autistic youth. 44 participants (22 ASD) aged 8 to 18 years, from the NIH funded longitudinal study on sex differences in autism were included in the analysis. Aggression was measured using the Child Behavior Checklist (CBCL), a parental report measure on problem behaviors, which includes items related to self aggression (self injurious behaviors) and other-aggression (aggression towards peers and adults). Data was collected at baseline and 3 to 8 years later. We expect low IQ and younger age will be related to higher aggressive scores on CBCL at baseline. We predict that youth with greater social improvement between timepoints and use of psychotropic medication will have lower levels of aggression over time. Identification of factors that impact changes in aggression over time can aid in implementing interventions to aggression and improve quality of life.

Attention deficit/hyperactivity disorder (ADHD) in girls had been largely under researched up until the 21st century, and still much is unknown or unclear about prevalence, symptomatology, associated impairments, longitudinal trajectories, treatment options, and treatment efficacy. In this study I attempt to characterize the ethnically diverse sample of adolescent girls (n=235) from the ADHD Teen Integrative Data Analysis Longitudinal (TIDAL) dataset (Sibley & Coxe, 2020). I investigate how different types of behavior therapy [engagement-focused (ENGAGE), comprehensive (COMP), standard (STANDARD), community-based usual care (UC), no treatment (NOTX)], medication engagement (consistent, inconsistent, negligible), clinical problem profile (simplex, internalizing, disruptive/disorganized), and family adversity predict changes in ADHD symptoms and related impairment (academic functioning, parent-teen conflict, and organizational functioning) over time. To do so I create a series of hierarchical linear regression models to examine the relationship between the predictive variables and the outcomes, and how each added variable affects the relationship using data from the ADHD TIDAL dataset. I predict an overall decline in symptoms and related impairment with the ADHD+internalizing profile predicting a greater decline than ADHD simplex and disruptive/disorganized ADHD. I also hypothesize that higher family adversity scores will predict a lesser decline in symptoms and related impairment. The results of this study will provide insight different into female presentations of ADHD. This information can then be used to optimize ADHD screening methods to reduce demographic disparities in ADHD and determine which combination of treatments are most effective for different subgroups.

Blast exposure via detonation of explosives results in symptoms such as mild traumatic brain injury, post-traumatic stress disorder, and chronic pain, serving as a major source of trauma for service members, Veterans, and civilian bystanders. These effects characterize the polytrauma clinical triad and pose a risk factor for increased substance use and substance use disorder (SUD). This polytrauma exposure yields diverse symptom trajectories. To understand the interactions between polytrauma and SUD risk, we use a rodent model that utilizes custom, in-house-built polysubstance self-administration chambers, Socially Integrated Polysubstance (SIP) cages, to measure water, alcohol, and fentanyl intake. Two types of tracking are used to monitor drinking: Radio Frequency Identification (RFID) tracking and the volumetric drinking monitor, and these combined tell us which mouse drinks what liquid for a variable period of time. These SIP cages have the advantage to study both voluntary drinking habits and preferences as well as the effect of group housing on these patterns. For this project, we used 69 C57Bl/6 male and female mice aged 9 weeks on arrival. These mice were then single or group-housed in the SIP cages for 9 days to monitor drinking patterns. Testing multiple substances at once can give us valuable insight into substance preference and polysubstance use, making it more representative of the human experience. These mice had behavioral testing before entrance into the SIP cages, and we will explore different methods to characterize these drinking and anxiety subgroups that emerge. In addition, we plan to look at sex differences and how that changes substance use and preference. These factors combined will give valuable insight into classifying substance use that can lead to more optimized treatment for Veterans with polytrauma.

FKBP51 is a protein that acts as a co-chaperone for glucocorticoid receptors and is active during the stress response. FKBP51 blunts glucocorticoid receptor signaling and can interfere with feedback inhibition of stress responses. Overall, increased levels of FKBP51 and its gene FKBP5 positively correlates with an increased risk of stress-related neuropsychiatric disorders. FKBP5 is expressed in serotonin neurons of the dorsal raphe nucleus (DRN), a brain region and system important to stress and anxiety responses. In order to investigate the function of FKBP5 in the DRN, new plasmids were generated to knock down or overexpress FKBP5, thereby changing FKBP51 expression in serotonin neurons. My first goal was to validate these plasmids using Neuro2A cells which endogenously express FKBP5. In order to do this, I cultured Neuro2A cells so that we could transfect the cells with either a CRISPR plasmid to decrease FKBP5 expression or an overexpression plasmid to increase FKBP5 expression. I used western blots to test for changes in FKBP51 protein, and that data was analyzed using integrated density in ImageJ. I found that the CRISPR knockdown plasmid successfully decreased expression of FKBP51 in cells and that the overexpression virus upregulated FKBP5. My second goal was to validate the CRISPR FKBP5 knockdown in vivo. Using Pet1-CRE mice that express Cre recombinase in serotonin neurons, we injected the CRISPR virus for a control virus into the DRN. I then used fluorescent in situ hybridization to look for changes in FKBP5 mRNA levels. I found that CRISPR successfully reduced FKBP5 relative to controls, indicating this virus is a viable way to reduce FKBP5 expression in vivo. This research is a clear step to better understanding stress-related neuropsychiatric disorders such as depression, anxiety, and PTSD.

Identifying risk factors for alcohol misuse among young adults is a critical public health priority given high rates of heavy drinking and alcohol-related consequences observed in this population. The field of behavioral economics has provided a set of quantifiable metrics that measure individuals’ demand for alcohol, which are important predictors of alcohol use, consequences, and response to treatment. Previous literature has also found that one’s self-reported drinking motives (e.g., drinking to cope with negative affect, to conform to peers, etc.) have important associations with drinking outcomes. Despite this literature, little is known regarding how one’s drinking motives relate to one’s demand. The study aims to investigate how different drinking motives may be differentially related to alcohol demand and whether birth sex moderates these relationships. The current study recruited 220 young adults (18-25 year-olds) from Washington state who report drinking at least twice a week and at least one recent heavy drinking episode (4+/5+ drinks for females/males). Participants completed online assessments that included the alcohol purchase task, which asked how many drinks they would hypothetically purchase and consume at various prices ranging from free to $20. Participants were also asked to report their birth sex and drinking motives (social, coping-anxiety, coping-depression, enhancement, conformity). I will conduct regression analyses to test for associations between drinking motives and alcohol demand, and to examine whether these associations are moderated by sex while controlling for age and discretionary spending. I hypothesize (1) stronger positive associations between coping motives and demand relative to other drinking motives, and (2) this relationship to be stronger for males. Results will improve our understanding of the relationship between drinking motives and demand between sexes and inform interventions focused on reducing alcohol misuse through alternate coping strategies or reducing demand.

Autism Spectrum Disorder (ASD), a neurodevelopmental disorder (NDD), has been increasingly associated with disruption of ion channel function. The symptoms and etiology of ASD are complex and associated with dysregulation of many brain regions. Recent research suggests that individuals with ASD have disrupted activity in the mesostriatal network, which is well-studied for its contribution to social behavior and social reward. Another developing area in the etiology of ASD are ion channel mutations. Specifically, the Kv7 ion channel family, encoded by the genes KCNQ1-5, have become increasingly implicated with NDDs such as ASD. Though broadly expressed throughout the nervous system, these channels are also expressed in the Ventral Tegmental Area (VTA), a region within the mesostriatal pathway that plays a key role in social behavior and social reward. Here we study the impact of a KCNQ3 mutation identified in multiple ASD patients, KCNQ3-R230C. To do this, we used transgenic mice and viral strategies to drive the expression of human wildtype (hKv7.3/WT) or mutant (hKv7.3/R2C) KCNQ3 in the VTA. I helped to conduct a three-chamber social interaction task wherein these transgenic mice could elect to interact with either a novel mouse or a familiar mouse, and I helped analyze the data therefrom. We observed a loss of social novelty preference in the three-chamber social interaction task in mice expressing hKv7.3/R2C but not in controls expressing hKv7.3/WT. This research contributes to our understanding of the role of ion channel disruptions in the VTA in the context of social behavior and ASD.

Alcohol use disorder affects 5.8% of adults in the U.S., incurring a yearly cost of $249 billion annually. The repeated and prolonged use of alcohol creates a variety of physiological and behavioral issues. Acute alcohol withdrawal syndrome encompasses seizures, delirium tremens, and in some cases, death. The dependence and withdrawal cycles lead to neuroinflammation, worsened withdrawal symptom severity, and impaired neuromodulation. The striatum plays an important role in the chronic aspect of addiction. This project focuses on how alcohol alters microglial function in this key brain region. At the Neumaier lab, we found that alcohol withdrawal increased the expression of genes involved in the unfolded protein response (UPR) in striatal microglia, the brain’s immune cells. The UPR is activated when there is an increase of misfolded proteins in the endoplasmic reticulum; which contribute to impaired cell function. The UPR is a protective mechanism in moderation, but when left unchecked, has been shown to increase cell death. We predict that removing CHOP will lead to a decrease in withdrawal symptoms and regulate the need to consume alcohol. Knocking out CHOP involves breeding CHOP fl/fl |Cx3cr1 CreER /eYFPI mice. We observe changes in the offspring via emotional behavioral tests after a 5 week period of CIE (chronic intermittent alcohol exposure). A second cohort’s brains are analyzed using cryosectioning and immunohistochemistry (IHC). My role is preparing the brains for analysis. The first step is removing and perfusing, which prepares the samples for cryosectioning. This is my other specialty, which is freezing and slicing the brains. Lastly, I conduct analysis with IHC, and look for physiological changes in the striatum. We anticipate our findings will have a positive and large impact on treating alcoholism. Our hope is to reduce the stigma surrounding addiction, and instead offer compassionate and scientifically based care.
 

Prosocial behavior is important to many species and its disruption is a hallmark symptom of many diseases and disorders including autism, schizophrenia, and depression. The neurotransmitter dopamine modulates neuronal activity in the nucleus accumbens (NAc) and plays a critical role in the regulation of prosocial behavior. While the role of dopamine (DA) is well studied in the context of social behavior, little is known about neuronal activity in the NAc during social behavior. Here we use transgenic mice, viral delivery of genetically encoded fluorescent calcium sensors, and a miniaturized microscope to measure NAc neuronal activity during a series of social behavior assays. We used the 3-chamber assay to investigate NAc encoding of social novelty preference, a 5 minute on-off free social interaction assay, and an operant social task in which mice press a lever to gain access to another mouse. Preliminary data suggests that the technique is feasible to detect neuronal activity in the NAc during social behavior, and that there is no detectable encoding of social novelty preference in the 3-chamber assay. Findings from this study will improve our understanding of how prosocial behavior is encoded and may lead to the development of treatments for diseases and disorders that result in a loss of prosocial behavior.

Concurrent fentanyl and methamphetamine use disorders are increasingly responsible for overdose deaths in America. Substance use disorders are driven, in part, by neuroplasticity within the cortico-basal ganglia-thalamic network. In particular, the striatum (i.e., the dorsal striatum and nucleus accumbens) functions as a central node contributing to drug-seeking and drug-taking behaviors. As individuals using opioids and psychostimulants together show high rates of overdose and relapse, it is essential to investigate how polysubstance stimulant-opioid use alters motivations for drug consumption and drug seeking. We will accomplish this by using a response dependent rodent model of fentanyl and methamphetamine self-administration (SA) that can directly assess specific behaviors related to addiction (drug-seeking, motivation, valuation). This SA model incorporates key components of the American Psychiatric Association’s diagnostic criteria for substance use disorders, including difficulty stopping or limiting drug intake (modeled by an escalation of drug intake), high motivation to obtain and consume drugs (modeled by a progressive ratio task), sustained drug craving during periods of abstinence (modeled by extinction), and relapse to drug consumption following abstinence (modeled by cue-induced reinstatement of drug seeking). For each of these behavioral metrics, we will compare rats with a history of chronic polysubstance use (i.e., methamphetamine and fentanyl SA) and rats with a history of chronic single substance use (i.e., either methamphetamine SA or fentanyl SA). We hypothesize that opioid-stimulant polysubstance use will have a unique, synergistic effect on addiction-related behaviors that is not present when either drug is used alone. In the future, we hope to investigate further the underlying neural circuits and striatal recruitment of polysubstance use disorders using this behavioral model. Accordingly, we believe this work has important implications for understanding how and why polysubstance use of opioids and stimulants drives continued drug use and increased relapse.

Veterans and Servicemembers experience trauma and chronic stress that lead to psychiatric disorders. Ample research has now demonstrated that blast exposure via detonation of high explosives on the battlefield can result in mild traumatic brain injury (mTBI) and it often occurs in combination with PTSD, depression, and addiction. Recently, Schindler Lab preliminarilly published that activation of dynorphin/kappa opioid receptor (KOR) system mediates stress/trauma-related dysphoria and anxiety-like outcomes. The expectation from this research project is that blast mTBI produces KOR activation to drive executive dysfunction and psychopathology and our aim is to understand the mechanisms underlying the adverse outcomes from blast-mTBI related to impaired executive functioning and determine the effect of blast trauma on the female and male population to understand sex as a biological variable. Prior to sham/blast exposure, mice will be injected with either vehicle (control) or norBNI that blocks activation of the KOR. Utilizing pneumatic shock tube and sophisticated operant paradigm in male and female mice, we modeled battle-field relevant open-field blast forces, detonation of high explosives to produce m-TBI and assessed various aspects of executive function (probability discounting, DRL, reversal learning, and progressive ratio) by monitoring the number and timing of lever presses and head entries into the food magazine of the operant chambers. Researching the chronic executive dysfunction mediated by blast-induced KOR activation during or immediately after repetitive blast exposure will contribute to understanding the underlying mechanisms regarding the effect of blast exposure on executive dysfunction for both females and males and the importance of timing on the effect to optimize further treatment options for veterans with an mTBI history and various psychiatric consequences. In the end, this research hopes to establish a novel understanding of mechanisms and treatment targets with experimental outcomes, giving rise to precision medicine approaches and endophenotype-specific treatment development.

The glymphatic system, which is primarily active during sleep, is a network of astroglial perivascular channels within the brain that allows for cerebrospinal fluid (CSF) influx and exchange. Glymphatic exchange plays a crucial role in the clearance of amyloid, a hallmark in the development of Alzheimer’s. Recently, a bidirectional relationship between Alzheimer's disease and sleep has also been suggested with amyloid deposition associated with mid-life sleep disruption. However, the mechanistic link between sleep disruption, particularly over chronic time scales, and the development of Alzheimer’s pathology remains unclear. This study investigated whether chronic sleep disruption, similar to that experienced in aging population, impacts downstream Alzheimer’s-related neuropathology. We hypothesized chronic sleep disruption will result in decreased glymphatic function and increased amyloid plaque burden. This experiment utilized a chronic sleep disruption model using Lafayette Sleep Fragmentation chambers, where mice underwent either chronic sleep disruption every two minutes during normal sleeping periods (daylight hours) or normal sleeping conditions (sham) from 10 weeks to 18 weeks of age (n=120). After eight weeks of sleep disruption or sham exposure, glymphatic function was assessed by dynamic in vivo near infrared imaging following stereotactic CSF tracer injection. Animals were perfusion fixed, cryosectioned, and glymphatic function was further assessed by measurement of fluorescent cerebrospinal fluid tracers in brain tissue. Aquaporin-4 localization, amyloid plaque deposition, and markers of astroglial and microglial activation were assessed by immunofluorescence. The collected data demonstrated that sleep disruption significantly increased neuropathological outcomes. The measured impact of glymphatic function was also correlated with these downstream pathological effects. These findings could be an indicator of interactions between neurological disease progression and an inflammatory expression after sleep disruption. They can also shed more light on the complex relationship between Alzheimer’s disease progression, the glymphatic system, and chronic sleep disruption.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and has been established as a risk factor for neurodegenerative diseases such as Alzheimer’s disease (AD). Neurofibrillary tangles (NFTs), aggregates of intracellular tau, are hallmarks of AD and are observed in the post-TBI brain; however, the mechanisms that contribute to tau aggregation and accumulation are not well understood. One key mechanism that may contribute to this tau aggregation is decreased clearance by the glymphatic system, a perivascular pathway that clears solutes, including tau, from the brain. PS19 mice with tau pathology were crossed with Aqp4-/- mice lacking the astroglial water channel aquaporin-4 (AQP4) or Snta1-/- mice lacking perivascular localization of AQP4. Behavioral tests were performed on the PS19:Aqp4 transgenic crosses at 4 or 6 months of age. Brain tissue was collected and stained for markers of phosphorylated-tau (p-tau) pathology. Sham or mild TBIs were performed on PS19:Snta1 transgenic crosses at 3 months of age. I performed behavioral testing at 4 months (1 month post-TBI) or 6 months (3 month post-TBI). Brain tissue was collected and stained for markers of p-tau pathology. I imaged this immunostained tissue and quantified the pathological tau burden. I observed that Aqp4 deletion was sufficient to exacerbate tau pathology in PS19 mice at 6 months old, in the absence of TBI, and more advanced tau pathology was observed in PS19+Snta1-/- mice at 6 months old (3 months post-TBI) compared to PS19+Snta1+/+ that also received a TBI. Loss of AQP4 or loss of perivascular AQP4 promotes tau pathology in a mouse model of tau pathology. These studies may provide a mechanistic basis for the vulnerability of the post-traumatic brain to tau aggregation and neurodegeneration and suggest that targeting glymphatic dysfunction may be useful in the prevention and treatment of neurodegeneration.

Type 1 Diabetes (T1D) is one of the most prevalent chronic diseases among teens in the United States. Teens with T1D facing socioeconomic disadvantage are disproportionately negatively affected by the burden of T1D and are at-risk for poor mental and physical health outcomes. Limited access to diabetes-related technology may be one factor contributing to these disparities. The purpose is to describe diabetes technology (continuous glucose monitors and insulin pumps) use among teens with T1D according to neighborhood-level socioeconomic disadvantage in Washington. The research also aims to investigate links between neighborhood disadvantage and diabetes outcomes and test whether diabetes technology moderates this relationship. We abstracted demographic, clinical, and psychosocial data from medical records of teens aged 13-18 seen for T1D clinical care at Seattle Children’s Hospital in 2019. We determined state-relative decile scores (1-10) for neighborhood disadvantage using the area deprivation index (ADI) tool, which considers income, education, employment, and housing quality factors. Diabetes management was measured using A1c, a 3-month average of blood sugar levels. Diabetes distress was measured using Problem Areas in Diabetes-Teen, a self-report measure of the emotional burden of living with diabetes. I will perform a descriptive analysis calculating the percentage of participants using diabetes technology for each ADI score and for low and high disadvantaged groups using cutoffs from previous literature to reveal technology use patterns. I will conduct linear regressions exploring relationships between neighborhood disadvantage and outcomes (A1c and diabetes distress) and enter diabetes technology as a moderator. We predict that higher neighborhood disadvantage will be associated with poorer diabetes management and higher distress, but this will vary as a function of technology use. Altogether, this research highlights use of a neighborhood-level tool to identify patterns for an at-risk group of teens and may help to identify intervention targets for public policy addressing health disparities.

Teacher burnout is a historical issue plaguing schools, but instead of school leadership focusing on decreasing teacher burdens, many teachers experience increased rates of burnout due to their focus being shifted to the added responsibilities to implement evidence-based practices (EBPs). Existing literature has shown that principals’ leadership type (i.e., transactional vs. transformational) and the implementation climate present (i.e., perceptions that EBP use is rewarded, expected, and supported) can impact teacher burnout. My research analyzes teacher burnout rates as they relate to leadership type and implementation climate when implementing Tier 1 (i.e., universal social, emotional, and behavioral programs and practices) services. As part of a larger ongoing study of a leadership-focused implementation strategy (i.e., strategies designed to improve adoption, fidelity, and impact of EBPs), principals, teachers, and school staff from 10 elementary schools within the same district completed a survey battery at the beginning of the school year. Data collected by the research team included things such as leadership type, implementation leadership, teacher burnout, and implementation climate. Preliminary analyses are ongoing to identify trends amongst school-building implementation leadership, leadership types, implementation climate, and teacher burnout when implementing Tier 1 EBPs, which can reveal how key implementation aspects relate to one another.