Browsing by Subject "Psychiatric disorders"
Now showing 1 - 10 of 14
Results Per Page
Sort Options
Item Human microRNA (miR-20b-5p) modulates Alzheimer's disease pathways and neuronal function, and a specific polymorphism close to the MIR20B gene influences Alzheimer's biomarkers(Springer Nature, 2022) Wang, Ruizhi; Chopra, Nipun; Nho, Kwangsik; Maloney, Bryan; Obukhov, Alexander G.; Nelson, Peter T.; Counts, Scott E.; Lahiri, Debomoy K.; Psychiatry, School of MedicineAlzheimer's disease (AD) is a progressive neurodegenerative disorder with loss of cognitive, executive, and other mental functions, and is the most common form of age-related dementia. Amyloid-β peptide (Aβ) contributes to the etiology and progression of the disease. Aβ is derived from the amyloid-β precursor protein (APP). Multiple microRNA (miRNA) species are also implicated in AD. We report that human hsa-miR20b-5p (miR-20b), produced from the MIR20B gene on Chromosome X, may play complex roles in AD pathogenesis, including Aβ regulation. Specifically, miR-20b-5p miRNA levels were altered in association with disease progression in three regions of the human brain: temporal neocortex, cerebellum, and posterior cingulate cortex. In cultured human neuronal cells, miR-20b-5p treatment interfered with calcium homeostasis, neurite outgrowth, and branchpoints. A single-nucleotide polymorphism (SNP) upstream of the MIR20B gene (rs13897515) associated with differences in levels of cerebrospinal fluid (CSF) Aβ1-42 and thickness of the entorhinal cortex. We located a miR-20b-5p binding site in the APP mRNA 3'-untranslated region (UTR), and treatment with miR-20b-5p reduced APP mRNA and protein levels. Network analysis of protein-protein interactions and gene coexpression revealed other important potential miR-20b-5p targets among AD-related proteins/genes. MiR-20b-5p, a miRNA that downregulated APP, was paradoxically associated with an increased risk for AD. However, miR-20b-5p also reduced, and the blockade of APP by siRNA likewise reduced calcium influx. As APP plays vital roles in neuronal health and does not exist solely to be the source of "pathogenic" Aβ, the molecular etiology of AD is likely to not just be a disease of "excess" but a disruption of delicate homeostasis.Item Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure(Springer Nature, 2023) Wong, Samantha A.; Lebois, Lauren A. M.; Ely, Timothy D.; van Rooij, Sanne J. H.; Bruce, Steven E.; Murty, Vishnu P.; Jovanovic, Tanja; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Bollen, Kenneth A.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Kurz, Michael C.; Swor, Robert A.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Pearson, Claire; Peak, David A.; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; O'Neil, Brian J.; Sergot, Paulina; Sanchez, Leon D.; Miller, Mark W.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C.; McLean, Samuel A.; Ressler, Kerry J.; Stevens, Jennifer S.; Harnett, Nathaniel G.; Emergency Medicine, School of MedicineChildhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [−0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.Item Lateral Orbitofrontal Cortex Encodes Presence of Risk and Subjective Risk Preference During Decision-Making(bioRxiv, 2024-04-09) Gabriel, Daniel B. K.; Havugimana, Felix; Liley, Anna E.; Aguilar, Ivan; Yeasin, Mohammed; Simon, Nicholas W.; Psychiatry, School of MedicineAdaptive decision-making requires consideration of objective risks and rewards associated with each option, as well as subjective preference for risky/safe alternatives. Inaccurate risk/reward estimations can engender excessive risk-taking, a central trait in many psychiatric disorders. The lateral orbitofrontal cortex (lOFC) has been linked to many disorders associated with excessively risky behavior and is ideally situated to mediate risky decision-making. Here, we used single-unit electrophysiology to measure neuronal activity from lOFC of freely moving rats performing in a punishment-based risky decision-making task. Subjects chose between a small, safe reward and a large reward associated with either 0% or 50% risk of concurrent punishment. lOFC activity repeatedly encoded current risk in the environment throughout the decision-making sequence, signaling risk before, during, and after a choice. In addition, lOFC encoded reward magnitude, although this information was only evident during action selection. A Random Forest classifier successfully used neural data accurately to predict the risk of punishment in any given trial, and the ability to predict choice via lOFC activity differentiated between and risk-preferring and risk-averse rats. Finally, risk preferring subjects demonstrated reduced lOFC encoding of risk and increased encoding of reward magnitude. These findings suggest lOFC may serve as a central decision-making hub in which external, environmental information converges with internal, subjective information to guide decision-making in the face of punishment risk.Item Longitudinal Patterns of Strengths Among Youth with Psychiatric Disorders: A Latent Profile Transition Analysis(Springer, 2021-07-13) Hong, Saahoon; Walton, Betty A.; Kim, Hea-Won; Lee, Sunkyung; Rhee, TaehoA better understanding of variability in the strengths of youth with psychiatric disorders is critical as a strength-based approach can lead to recovery. This study aimed to identify subgroups of strengths among youth with mental disorders and determine whether subgroups changes were associated with mental health recovery. Youth with mental disorders (N = 2228) from a statewide database were identified in the state fiscal year of 2019. Using the latent profile analysis and latent transition analysis, we identified three strength profiles (i.e., essential, usable, and buildable). Over 90% of youth sustained or developed strengths over time. Positive transitions were associated with mental health recovery, symptom reduction, and personal recovery. Buildable strengths supported youth’s personal recovery independent of improving mental health needs. The findings suggest that subgroups of strengths may be a promising source for planning and tracking youth’s progress and guiding clinicians to more efficiently allocate community-based resources.Item Olfactory Reference Syndrome: A Case Report and Screening Tool(Springer, 2020-04) Chernyak, Yelena; Chapleau, Kristine M.; Tanious, Shariff F.; Dattilo, Natalie C.; Diaz, David R.; Landsberger, Sarah A.Olfactory reference syndrome (ORS) is a lesser known disorder that is related to obsessive–compulsive disorder. ORS is the obsessional and inaccurate belief that one is emitting a foul odor leading to embarrassment or concern about offending others, excessive hygiene behaviors, and social avoidance that significantly interferes with daily functioning. Although ORS is rare, it is challenging to diagnose. ORS-sufferers first seek treatment from non- psychiatric providers (e.g., dermatologists, dentists.) to alleviate the perceived odor, which frequently leads to misdiagnosis and unnecessary treatments. Additionally, because ORS-sufferers can have limited insight and ideas of reference, they can be misdiagnosed as having a psychotic or delusional disorder. We present a case report of a 42-year-old woman with ORS, and how the correct diagnosis of ORS provided with psychiatric treatment led to significant improvement in her daily functioning. We provide a literature review on the disorder as well as a short screener to assess ORS.Item Perceived Mental Illness Stigma Among Youth in Psychiatric Outpatient Treatment(Sage, 2012-03) Elkington, Katherine S.; Hackler, Dusty; McKinnon, Karen; Borges, Cristiane; Wright, Eric R.; Wainberg, Milton L.; Sociology, School of Liberal ArtsThis research explores the experiences of mental illness stigma in 24 youth (58.3% male, 13–24 years, 75% Latino) in psychiatric outpatient treatment. Using Link and Phelan’s (2001) model of stigmatization, we conducted thematic analysis of the interview texts, examining experiences of stigma at individual and structural levels, in addition to the youths’ social-psychological processes. Youth in psychiatric treatment acknowledged that their larger cultural context holds pejorative viewpoints toward those with mental illness and reported experiences of stigma within their families and social networks. Our results also offer insight into the social-psychological processes of stigma, highlighting how labeling may influence their self-concept and the strategies in which youth engage to manage a stigmatized identity. We discuss differences in stigma experiences by gender, age, and diagnosis. Findings provide new information on the stigma experiences of youth in psychiatric treatment and suggest that a multilevel approach to reduce stigma is warranted.Item Perspective on Beyond Statistical Significance: Finding Meaningful Effects(Karger, 2021) Edenberg, Howard J.; Biochemistry and Molecular Biology, School of MedicineItem Psychiatric symptoms and their association with sleep disturbances in intensive care unit survivors(Dovepress, 2019-03-22) Wang, Sophia; Meeker, Jared W.; Perkins, Anthony J.; Gao, Sujuan; Khan, Sikandar H.; Sigua, Ninotchka L.; Manchanda, Shalini; Boustani, Malaz A.; Khan, Babar A.; Psychiatry, School of MedicineBackground: Sleep disturbances in critically ill patients are associated with poorer long-term clinical outcomes and quality of life. Studies are needed to better characterize associations and risk factors for persistent sleep disturbances after intensive care unit (ICU) discharge. Psychiatric disorders are frequently associated with sleep disturbances, but the role of psychiatric symptoms in sleep disturbances in ICU survivors has not been well-studied. Objective: To examine the association between psychiatric symptoms and sleep disturbances in ICU survivors. Methods: 112 adult ICU survivors seen from July 2011 to August 2016 in the Critical Care Recovery Center, an ICU survivor clinic at the Eskenazi Hospital in Indianapolis, IN, USA, were assessed for sleep disturbances (insomnia, hypersomnia, difficulty with sleep onset, difficulty with sleep maintenance, and excessive daytime sleepiness) and psychiatric symptoms (trauma-related symptoms and moderate to severe depressive symptoms) 3 months after ICU discharge. A multivariate logistic regression model was performed to examine the association between psychiatric symptoms and sleep disturbances. Analyses were controlled for age, hypertension, history of depression, and respiratory failure. Results: ICU survivors with both trauma-related and depression symptoms (OR 16.66, 95% CI 2.89-96.00) and trauma-related symptoms alone (OR 4.59, 95% CI 1.11-18.88) had a higher likelihood of sleep disturbances. Depression symptoms alone were no longer significantly associated with sleep disturbances when analysis was controlled for trauma-related symptoms. Conclusion: Trauma-related symptoms and trauma-related plus moderate to severe depressive symptoms were associated with a higher likelihood of sleep disturbances. Future studies are needed to determine whether psychiatric symptoms are associated with objective changes on polysomnography and actigraphy and whether adequate treatment of psychiatric symptoms can improve sleep disturbances.Item Repeated electromagnetic field stimulation lowers amyloid-β peptide levels in primary human mixed brain tissue cultures(Springer Nature, 2021-01-12) Perez, Felipe P.; Maloney, Bryan; Chopra, Nipun; Morisaki, Jorge J.; Lahiri, Debomoy K.; Medicine, School of MedicineLate Onset Alzheimer’s Disease is the most common cause of dementia, characterized by extracellular deposition of plaques primarily of amyloid-β (Aβ) peptide and tangles primarily of hyperphosphorylated tau protein. We present data to suggest a noninvasive strategy to decrease potentially toxic Aβ levels, using repeated electromagnetic field stimulation (REMFS) in primary human brain (PHB) cultures. We examined effects of REMFS on Aβ levels (Aβ40 and Aβ42, that are 40 or 42 amino acid residues in length, respectively) in PHB cultures at different frequencies, powers, and specific absorption rates (SAR). PHB cultures at day in vitro 7 (DIV7) treated with 64 MHz, and 1 hour daily for 14 days (DIV 21) had significantly reduced levels of secreted Aβ40 (p = 001) and Aβ42 (p = 0.029) peptides, compared to untreated cultures. PHB cultures (DIV7) treated at 64 MHz, for 1 or 2 hour during 14 days also produced significantly lower Aβ levels. PHB cultures (DIV28) treated with 64 MHz 1 hour/day during 4 or 8 days produced a similar significant reduction in Aβ40 levels. 0.4 W/kg was the minimum SAR required to produce a biological effect. Exposure did not result in cellular toxicity nor significant changes in secreted Aβ precursor protein-α (sAPPα) levels, suggesting the decrease in Aβ did not likely result from redirection toward the α-secretase pathway. EMF frequency and power used in our work is utilized in human magnetic resonance imaging (MRI, thus suggesting REMFS can be further developed in clinical settings to modulate Aβ deposition.Item Rivastigmine modifies the α-secretase pathway and potentially early Alzheimer's disease(Springer Nature, 2020-02) Ray, Balmiki; Maloney, Bryan; Sambamurti, Kumar; Karnati, Hanuma K.; Nelson, Peter T.; Greig, Nigel H.; Lahiri, Debomoy K.; Psychiatry, School of MedicineRivastigmine (or Exelon) is a cholinesterase inhibitor, currently used as a symptomatic treatment for mild-to-moderate Alzheimer’s disease (AD). Amyloid-β peptide (Aβ) generated from its precursor protein (APP) by β-secretase (or BACE1) and γ-secretase endoproteolysis. Alternative APP cleavage by α-secretase (a family of membrane-bound metalloproteases– Adamalysins) precludes the generation of toxic Aβ and yields a neuroprotective and neurotrophic secreted sAPPα fragment. Several signal transduction pathways, including protein kinase C and MAP kinase, stimulate α-secretase. We present data to suggest that rivastigmine, in addition to anticholinesterase activity, directs APP processing away from BACE1 and towards α-secretases. We treated rat neuronal PC12 cells and primary human brain (PHB) cultures with rivastigmine and the α-secretase inhibitor TAPI and assayed for levels of APP processing products and α-secretases. We subsequently treated 3×Tg (transgenic) mice with rivastigmine and harvested hippocampi to assay for levels of APP processing products. We also assayed postmortem human control, AD, and AD brains from subjects treated with rivastigmine for levels of APP metabolites. Rivastigmine dose-dependently promoted α-secretase activity by upregulating levels of ADAM-9, -10, and -17 α-secretases in PHB cultures. Co-treatment with TAPI eliminated rivastigmine-induced sAPPα elevation. Rivastigmine treatment elevated levels of sAPPα in 3×Tg mice. Consistent with these results, we also found elevated sAPPα in postmortem brain samples from AD patients treated with rivastigmine. Rivastigmine can modify the levels of several shedding proteins and directs APP processing toward the non-amyloidogenic pathway. This novel property of rivastigmine can be therapeutically exploited for disease-modifying intervention that goes beyond symptomatic treatment for AD.