Browsing by Subject "Psychiatric disorders"
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Item An interlocked oscillator model for high-frequency firing of the midbrain dopaminergic neuron(Springer Nature, 2011-07-18) Kuznetsov, Alexey; Ha, Joon; Mathematical Sciences, School of ScienceItem Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research(Springer Nature, 2025) Cai, Na; Verhulst, Brad; Andreassen, Ole A.; Buitelaar, Jan; Edenberg, Howard J.; Hettema, John M.; Gandal, Michael; Grotzinger, Andrew; Jonas, Katherine; Lee, Phil; Mallard, Travis T.; Mattheisen, Manuel; Neale, Michael C.; Nurnberger, John I., Jr.; Peyrot, Wouter J.; Tucker-Drob, Elliot M.; Smoller, Jordan W.; Kendler, Kenneth S.; Biochemistry and Molecular Biology, School of MedicinePsychiatric disorders are highly comorbid, heritable, and genetically correlated [1-4]. The primary objective of cross-disorder psychiatric genetics research is to identify and characterize both the shared genetic factors that contribute to convergent disease etiologies and the unique genetic factors that distinguish between disorders [4, 5]. This information can illuminate the biological mechanisms underlying comorbid presentations of psychopathology, improve nosology and prediction of illness risk and trajectories, and aid the development of more effective and targeted interventions. In this review we discuss how estimates of comorbidity and identification of shared genetic loci between disorders can be influenced by how disorders are measured (phenotypic assessment) and the inclusion or exclusion criteria in individual genetic studies (sample ascertainment). Specifically, the depth of measurement, source of diagnosis, and time frame of disease trajectory have major implications for the clinical validity of the assessed phenotypes. Further, biases introduced in the ascertainment of both cases and controls can inflate or reduce estimates of genetic correlations. The impact of these design choices may have important implications for large meta-analyses of cohorts from diverse populations that use different forms of assessment and inclusion criteria, and subsequent cross-disorder analyses thereof. We review how assessment and ascertainment affect genetic findings in both univariate and multivariate analyses and conclude with recommendations for addressing them in future research.Item Correction: Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research(Springer Nature, 2025) Cai, Na; Verhulst, Brad; Andreassen, Ole A.; Buitelaar, Jan; Edenberg, Howard J.; Hettema, John M.; Gandal, Michael; Grotzinger, Andrew; Jonas, Katherine; Lee, Phil; Mallard, Travis T.; Mattheisen, Manuel; Neale, Michael C.; Nurnberger, John I., Jr.; Peyrot, Wouter J.; Tucker-Drob, Elliot M.; Smoller, Jordan W.; Kendler, Kenneth S.; Biochemistry and Molecular Biology, School of MedicineCorrection to: Molecular Psychiatry 10.1038/s41380-024-02878-x, published online 27 December 2024 In this article the author’s name Wouter J. Peyrot was incorrectly written as Wouter Peyrout. The original article has been corrected.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 Perceived mental illness stigma, intimate relationships and sexual risk behavior in youth with mental illness(Sage, 2013) Elkington, Katherine S.; Hackler, Dusty; Walsh, Tracy A.; Latack, Jessica A.; McKinnon, Karen; Borges, Cristiane; Wright, Eric R.; Wainberg, Milton L.; Health Policy and Management, Richard M. Fairbanks School of Public HealthThe current study examines the role of mental illness-related stigma on romantic or sexual relationships and sexual behavior among youth with mental illness (MI), including youths' experiences of stigma, the internalization of these experiences, and the behavior associated with managing stigma within romantic and sexual relationships. We conducted in-depth interviews with N=20 youth with mental illness (MI) (55% male, 16-24 years, 75% Latino) from 4 psychiatric outpatient clinics in New York City. We conducted a thematic analysis to investigate shared experiences of MI stigma and its impact on youth's sexual or romantic relationships and associated behaviors. Our analysis revealed four main themes: 1) societal perceptions of those with MI as partners (societal stigma); 2) individual experiences of stigma within relationships (individual level); 3) internalized stigma of self as a partner (social-psychological processes); and 4) managing a stigmatized identity, of which some of the behaviors directly placed them at increased risk for HIV. We found that just under half of the sample (n=9/20) endorsed all themes, including engaging in HIV/STI sexual risk behaviors as a method to manage a stigmatize identity, which suggests that MI stigma and sexual risk may be linked. We discuss differences by gender and diagnosis. Findings provide new information for providers and researchers to address on the role of stigma experiences in the romantic and sexual behavior of youth in psychiatric treatment. Implications for stigma and HIV/STI prevention interventions are discussed.