Browsing by Author "Psychiatry, School of Medicine"
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Item 21st-Century Genetics in Psychiatric Residency Training: How Do We Get There?(American Medical Association, 2019-03-01) Besterman, Aaron D.; Moreno-De-Luca, Daniel; Nurnberger, John I., Jr.; Psychiatry, School of MedicineItem 39. Viruses and Schizophrenia: Implications for Pathophysiology and Treatment(Oxford University Press, 2018-04) Breier, Alan; Psychiatry, School of MedicineOverall Abstract: The viral hypothesis of schizophrenia posits that viral infections disrupts cortical circuits that give rise to schizophrenia psychopathology. Prenatal viral exposure during key neurodevelopmental periods, either through direct effects on fetal brain or exposure to excessive maternal cytokines and other chemokines, have been implicated. In addition, abnormal activation of dormant neuro-viruses have been linked to the pathophysiology of schizophrenia. Activation of dormant viruses has potentially important treatment implication for therapies, such as valacyclovir, that suppress viral activity. Among the viruses that have been mostly frequently associated with schizophrenia include herpes simplex virus type 1 (HSV1) and Epstein-Barr virus (EBV). The purpose of this symposium is to focus on the role of viruses in the pathophysiology of schizophrenia and results of antiviral treatment trials in this illness.Item 501 Maternal PTSD and Child Brain Function During Implicit Emotion Regulation(Cambridge University Press, 2024-04-03) Crum, Kathleen I.; Aloi, Joseph; LeFevre, Katherine; McCormack, Kennedy; Hulvershorn, Leslie; Psychiatry, School of MedicineOBJECTIVES/GOALS: Maternal mental health, such as post-traumatic stress disorder (PTSD), is closely linked to child mental health. PTSD in mothers is associated with their children’s emotional responses. We examined associations between maternal PTSD and child brain function during emotion regulation. METHODS/STUDY POPULATION: Eight children ages 10-12 years, whose mothers had trauma histories, performed the Emotional N-Back task during functional MRI scanning. Mothers and children each reported on their trauma exposure and PTSD symptom severity. BOLD response to fearful faces during the Emotional N-Back was extracted from two specific brain regions of interest, amygdala and anterior cingulate cortex. These regions are involved in emotional response and attentional control, which are processes intrinsic to emotion regulation. An independent samples t-test was conducted on children’s BOLD response to fearful faces, with maternal PTSD symptom severity (high, low) as the independent variable. A parallel analysis was conducted with child PTSD symptom severity (high, low) as the independent variable. RESULTS/ANTICIPATED RESULTS: We found a main effect of maternal PTSD within brain regions of relevance to implicit emotion regulation. Compared to children whose mothers reported low PTSD symptom severity (n=4), children whose mothers reported high PTSD symptom severity (n=4) showed greater responsiveness to fearful faces in anterior cingulate cortex (t=2.04, p=.09,d=1.44) and amygdala (t=2.44, p=.05, d=1.72) at trending significance. A parallel analysis with child PTSD symptom severity showed no differences in brain function by this factor (ps=.55-.61). DISCUSSION/SIGNIFICANCE: Our pilot study is the first, to our knowledge, to examine associations between maternal PTSD and brain function during emotion regulation in their children. This study lays a foundation for future work; our goal is to explore dysfunction in emotion regulation neurocircuitry as one mechanism linking maternal PTSD to their children’s mental health.Item 58896 Feasibility of a Parent Navigator Program for Parents of Justice-Involved Youth(Cambridge University Press, 2021-03-30) Dir, Allyson L.; Wiehe, Sarah; Aalsma, Matthew C.; Psychiatry, School of MedicineABSTRACT IMPACT: Development and implementation of a parent navigator program to help parents of justice-involved youth could assist parents in navigating the justice system, improve engagement with court and probation, and ultimately improve outcomes for youth involved in the juvenile justice system OBJECTIVES/GOALS: The goals of the study are to (1) develop a parent-peer navigator program utilizing community-based participatory design; and (2) implement and assess the feasibility of a parent peer navigator program in an urban juvenile justice system. METHODS/STUDY POPULATION: The EPIS framework will guide development and implementation of the navigator program as well as measurement of the implementation process, including measurements of feasibility and acceptability. In the Exploration phase, qualitative interviews with juvenile justice staff, parents of justice-involved youth, and members of the local family advisory board will inform program needs. In the preparation stage, I will work closely with the family advisory board to develop the actual parent navigator program protocol, including a training plan for navigators and their specific roles. I will conduct an open trial in the implementation phase, measuring program feasibility and acceptability among parents, navigators, juvenile justice staff, parents, and youth utilizing mixed methods. RESULTS/ANTICIPATED RESULTS: Results will inform feasibility of implementing the program as well as acceptability of the program based on mixed methods data from parents of justice-involved youth, juvenile justice staff, family advisory board members, and other community stakeholders. Results will potentially inform conduct of a larger scale pilot hybrid implementation-effectiveness study. DISCUSSION/SIGNIFICANCE OF FINDINGS: Development and implementation of a parent navigator program to help parents of justice-involved youth could assist parents in navigating the justice system, improve engagement with court and probation, and ultimately improve outcomes for youth involved in the juvenile justice system.Item A classification system for youth outpatient behavioral health services billed to medicaid(Frontiers Media, 2024-02-05) Rodríguez, Gabriela M.; Pederson, Casey A.; Garcia, Dainelys; Schwartz, Katherine; Brown, Steven A.; Aalsma, Matthew C.; Psychiatry, School of MedicineRates of youth behavioral health concerns have been steadily rising. Administrative data can be used to study behavioral health service utilization among youth, but current methods that rely on identifying an associated behavioral health diagnosis or provider specialty are limited. We reviewed all procedure codes billed to Medicaid for youth in one U.S. county over a 10-year period. We identified 158 outpatient behavioral health procedure codes and classified them according to service type. This classification system can be used by health services researchers to better characterize youth behavioral health service utilization.Item A locus at 19q13.31 significantly reduces the ApoE ε4 risk for Alzheimer's Disease in African Ancestry(Public Library of Science, 2022-07-05) Rajabli, Farid; Beecham, Gary W.; Hendrie, Hugh C.; Baiyewu, Olusegun; Ogunniyi, Adesola; Gao, Sujuan; Kushch, Nicholas A.; Lipkin-Vasquez, Marina; Hamilton-Nelson, Kara L.; Young, Juan I.; Dykxhoorn, Derek M.; Nuytemans, Karen; Kunkle, Brian W.; Wang, Liyong; Jin, Fulai; Liu, Xiaoxiao; Feliciano-Astacio, Briseida E.; Alzheimer’s Disease Sequencing Project; Alzheimer’s Disease Genetic Consortium; Schellenberg, Gerard D.; Dalgard, Clifton L.; Griswold, Anthony J.; Byrd, Goldie S.; Reitz, Christiane; Cuccaro, Michael L.; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Vance, Jeffery M.; Psychiatry, School of MedicineAfrican descent populations have a lower Alzheimer disease risk from ApoE ε4 compared to other populations. Ancestry analysis showed that the difference in risk between African and European populations lies in the ancestral genomic background surrounding the ApoE locus (local ancestry). Identifying the mechanism(s) of this protection could lead to greater insight into the etiology of Alzheimer disease and more personalized therapeutic intervention. Our objective is to follow up the local ancestry finding and identify the genetic variants that drive this risk difference and result in a lower risk for developing Alzheimer disease in African ancestry populations. We performed association analyses using a logistic regression model with the ApoE ε4 allele as an interaction term and adjusted for genome-wide ancestry, age, and sex. Discovery analysis included imputed SNP data of 1,850 Alzheimer disease and 4,331 cognitively intact African American individuals. We performed replication analyses on 63 whole genome sequenced Alzheimer disease and 648 cognitively intact Ibadan individuals. Additionally, we reproduced results using whole-genome sequencing of 273 Alzheimer disease and 275 cognitively intact admixed Puerto Rican individuals. A further comparison was done with SNP imputation from an additional 8,463 Alzheimer disease and 11,365 cognitively intact non-Hispanic White individuals. We identified a significant interaction between the ApoE ε4 allele and the SNP rs10423769_A allele, (β = -0.54,SE = 0.12,p-value = 7.50x10-6) in the discovery data set, and replicated this finding in Ibadan (β = -1.32,SE = 0.52,p-value = 1.15x10-2) and Puerto Rican (β = -1.27,SE = 0.64,p-value = 4.91x10-2) individuals. The non-Hispanic Whites analyses showed an interaction trending in the "protective" direction but failing to pass a 0.05 significance threshold (β = -1.51,SE = 0.84,p-value = 7.26x10-2). The presence of the rs10423769_A allele reduces the odds ratio for Alzheimer disease risk from 7.2 for ApoE ε4/ε4 carriers lacking the A allele to 2.1 for ApoE ε4/ε4 carriers with at least one A allele. This locus is located approximately 2 mB upstream of the ApoE locus, in a large cluster of pregnancy specific beta-1 glycoproteins on chromosome 19 and lies within a long noncoding RNA, ENSG00000282943. This study identified a new African-ancestry specific locus that reduces the risk effect of ApoE ε4 for developing Alzheimer disease. The mechanism of the interaction with ApoEε4 is not known but suggests a novel mechanism for reducing the risk for ε4 carriers opening the possibility for potential ancestry-specific therapeutic intervention.Item A Patient-Centered Nurse-Supported Primary care-based Collaborative Care Program to Treat Opioid Use Disorder and Depression: Design and Protocol for the MI-CARE Randomized Controlled Trial(Elsevier, 2023) DeBar, Lynn L.; Bushey, Michael A.; Kroenke, Kurt; Bobb, Jennifer F.; Schoenbaum, Michael; Thompson, Ella E.; Justice, Morgan; Zatzick, Douglas; Hamilton, Leah K.; McMullen, Carmit K.; Hallgren, Kevin A.; Benes, Lindsay L.; Forman, David P.; Caldeiro, Ryan M.; Brown, Ryan P.; Campbell, Noll L.; Anderson, Melissa L.; Son, Sungtaek; Haggstrom, David A.; Whiteside, Lauren; Schleyer, Titus K. L.; Bradley, Katharine A.; Psychiatry, School of MedicineBackground: Opioid use disorder (OUD) contributes to rising morbidity and mortality. Life-saving OUD treatments can be provided in primary care but most patients with OUD don't receive treatment. Comorbid depression and other conditions complicate OUD management, especially in primary care. The MI-CARE trial is a pragmatic randomized encouragement (Zelen) trial testing whether offering collaborative care (CC) to patients with OUD and clinically-significant depressive symptoms increases OUD medication treatment with buprenorphine and improves depression outcomes compared to usual care. Methods: Adult primary care patients with OUD and depressive symptoms (n ≥ 800) from two statewide health systems: Kaiser Permanente Washington and Indiana University Health are identified with computer algorithms from electronic Health record (EHR) data and automatically enrolled. A random sub-sample (50%) of eligible patients is offered the MI-CARE intervention: a 12-month nurse-driven CC intervention that includes motivational interviewing and behavioral activation. The remaining 50% of the study cohort comprise the usual care comparison group and is never contacted. The primary outcome is days of buprenorphine treatment provided during the intervention period. The powered secondary outcome is change in Patient Health Questionnaire (PHQ)-9 depression scores. Both outcomes are obtained from secondary electronic healthcare sources and compared in "intent-to-treat" analyses. Conclusion: MI-CARE addresses the need for rigorous encouragement trials to evaluate benefits of offering CC to generalizable samples of patients with OUD and mental health conditions identified from EHRs, as they would be in practice, and comparing outcomes to usual primary care. We describe the design and implementation of the trial, currently underway.Item A pilot randomized controlled trial comparing a novel compassion and metacognition approach for schizotypal personality disorder with a combination of cognitive therapy and psychopharmacological treatment(BMC, 2023-02-20) Cheli, Simone; Cavalletti, Veronica; Lysaker, Paul H.; Dimaggio, Giancarlo; Petrocchi, Nicola; Chiarello, Francesca; Enzo, Consuelo; Velicogna, Francesco; Mancini, Francesco; Goldzweig, Gil; Psychiatry, School of MedicineBackground: Schizotypal personality disorder is characterized by a pervasive pattern of maladaptive behavior that has been associated with the liability for schizophrenia. Little is known about effective psychosocial interventions. This pilot non-inferiority randomized controlled trial aimed to compare a novel form of psychotherapy tailored for this disorder and a combination of cognitive therapy and psychopharmacological treatment. The former treatment - namely, Evolutionary Systems Therapy for Schizotypy-integrated evolutionary, metacognitively oriented, and compassion focused approaches. Methods: Thirty-three participants were assessed for eligibility, twenty-four randomized on a 1:1 ratio, nineteen included in the final analysis. The treatments lasted 6 months (24 sessions). The primary outcome was change across nine measurements in personality pathology, the secondary outcomes were remission from diagnosis and pre-post changes in general symptomatology and metacognition. Results: Primary outcome suggested a non-inferiority of the experimental treatment in respect to control condition. Secondary outcomes reported mixed results. There was no significant difference in terms of remission, but experimental treatment showed a larger reduction of general symptomatology (η2 = 0.558) and a larger increase in metacognition (η2 = 0.734). Conclusions: This pilot study reported promising results about the effectiveness of the proposed novel approach. A confirmatory trial on large sample size is needed to provide evidence about relative effectiveness of the two treatment conditions.Item A pilot study of participatory video in early psychosis: Qualitative findings(PAGEPress, 2022-10-04) MacDougall, Arlene G.; Price, Elizabeth; Glen, Sarah; Wiener, Joshua C.; Kukan, Sahana; Powe, Laura; Bird, Richelle; Lysaker, Paul H.; Anderson, Kelly K.; Norman, Ross M. G.; Psychiatry, School of MedicineFor people with psychotic disorders, developing a personal narrative about one’s experiences with psychosis can help promote recovery. This pilot study examined participants’ reactions to and experiences of participatory video as an intervention to help facilitate recovery-oriented narrative development in early psychosis. Outpatients of an early psychosis intervention program were recruited to participate in workshops producing short documentary-style videos of their collective and individual experiences. Six male participants completed the program and took part in a focus group upon completion and in an individual semistructured interview three months later. Themes were identified from the focus group and interviews and then summarized for descriptive purposes. Prominent themes included impacts of the videos on the participants and perceived impacts on others, fulfilment from sharing experiences and expressing oneself, value of collaboration and cohesion in a group, acquiring interpersonal and technological skills, and recommendations for future implementation. Findings of this study suggest that participatory video is an engaging means of self-definition and self-expression among young people in recovery from early psychosis.Item A preliminary choroid plexus volumetric study in individuals with psychosis(Wiley, 2023) Senay, Olcay; Seethaler, Magdalena; Makris, Nikos; Yeterian, Edward; Rushmore, Jarrett; Cho, Kang Ik K.; Rizzoni, Elizabeth; Heller, Carina; Pasternak, Ofer; Szczepankiewicz, Filip; Westin, Carl-Frederik; Losak, Jan; Ustohal, Libor; Tomandl, Josef; Vojtisek, Lubomir; Kudlicka, Peter; Kikinis, Zora; Holt, Daphne; Lewandowski, Kathryn E.; Lizano, Paulo; Keshavan, Matcheri S.; Öngür, Dost; Kasparek, Tomas; Breier, Alan; Shenton, Martha E.; Seitz-Holland, Johanna; Kubicki, Marek; Psychiatry, School of MedicineThe choroid plexus (ChP) is part of the blood‐cerebrospinal fluid barrier, regulating brain homeostasis and the brain's response to peripheral events. Its upregulation and enlargement are considered essential in psychosis. However, the timing of the ChP enlargement has not been established. This study introduces a novel magnetic resonance imaging‐based segmentation method to examine ChP volumes in two cohorts of individuals with psychosis. The first sample consists of 41 individuals with early course psychosis (mean duration of illness = 1.78 years) and 30 healthy individuals. The second sample consists of 30 individuals with chronic psychosis (mean duration of illness = 7.96 years) and 34 healthy individuals. We utilized manual segmentation to measure ChP volumes. We applied ANCOVAs to compare normalized ChP volumes between groups and partial correlations to investigate the relationship between ChP, LV volumes, and clinical characteristics. Our segmentation demonstrated good reliability (.87). We further showed a significant ChP volume increase in early psychosis (left: p < .00010, right: p < .00010) and a significant positive correlation between higher ChP and higher LV volumes in chronic psychosis (left: r = .54, p = .0030, right: r = .68; p < .0010). Our study suggests that ChP enlargement may be a marker of acute response around disease onset. It might also play a modulatory role in the chronic enlargement of lateral ventricles, often reported in psychosis. Future longitudinal studies should investigate the dynamics of ChP enlargement as a promising marker for novel therapeutic strategies.