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Item Gut and brain profiles that resemble pre-motor and early-stage Parkinson’s disease in methamphetamine self-administering rats(Elsevier, 2021) Persons, Amanda L.; Bradaric, Brinda D.; Kelly, Leo P.; Kousik, Sharanya M.; Graves, Steven M.; Yamamoto, Bryan K.; Napier, T. Celeste; Pharmacology and Toxicology, School of MedicineIntroduction: Methamphetamine is a potent psychomotor stimulant, and methamphetamine abusers are up to three times more likely to develop Parkinson's disease (PD) later in life. Prodromal PD may involve gut inflammation and the accumulation of toxic proteins that are transported from the enteric nervous system to the central nervous system to mediate, in part, the degeneration of dopaminergic projections. We hypothesized that self-administration of methamphetamine in rats produces a gut and brain profile that mirrors pre-motor and early-stage PD. Methods: Rats self-administered methamphetamine in daily 3 h sessions for two weeks. Motor function was assessed before self-administration, during self-administration and throughout the 56 days of forced abstinence. Assays for pathogenic markers (tyrosine hydroxylase, glial fibrillary acidic protein (GFAP), α-synuclein) were conducted on brain and gut tissue collected at one or 56 days after cessation of methamphetamine self-administration. Results: Motor deficits emerged by day 14 of forced abstinence and progressively worsened up to 56 days of forced abstinence. In the pre-motor stage, we observed increased immunoreactivity for GFAP and α-synuclein within the ganglia of the myenteric plexus in the distal colon. Increased α-synuclein was also observed in the substantia nigra pars compacta. At 56 days, GFAP and α-synuclein normalized in the gut, but the accumulation of nigral α-synuclein persisted, and the dorsolateral striatum exhibited a significant loss of tyrosine hydroxylase. Conclusion: The pre-motor profile is consistent with gut inflammation and gut/brain α-synuclein accumulation associated with prodromal PD and the eventual development of the neurological disease.Item Trends of Cocaine Use and Manifestations in Hospitalized Patients: A Cross-Sectional Study(Cureus, 2022-02-10) Gangu, Karthik; Bobba, Aniesh; Basida, Sanket D.; Avula, Sindhu; Chela, Harleen; Singh, Simranjit; Medicine, School of MedicineObjective: About 41 million people aged ≥18 years reported lifetime use of cocaine, and 5.4 million people reported having used cocaine in 2019. We aim to identify trends of cocaine use, manifestations, concomitant drug use, and financial burden on health care among hospitalized patients. Methods: We utilized National Inpatient Sample from years 2006-2018. Patients with age ≥18 years, admitted to the hospital with a diagnosis of cocaine abuse, dependence, poisoning, or unspecified cocaine use were included in the study. We used ICD-9 Clinical Modification (CM) and ICD-10-CM codes to retrieve patient samples and comorbid conditions. The primary outcome was the trend in cocaine use among hospitalized patients from the year 2006 to 2018. Cochran-Mantel-Haenszel test was used to assess the significance of trends. Results: In the year 2006, the prevalence of cocaine abuse among hospitalized patients was 10,751 per million with an initial decline to 7,451 per million in 2012 and a subsequent increase to 11,891 per million hospitalized patients in 2018 with p =0.01. The majority of patients admitted were older than 50 years (43.27%), and a greater percentage of patients were males. All ethnicities showed a rising trend in the use of cocaine except for Native Americans. Cardiovascular effects, neuropsychiatric and infectious manifestations in hospitalized patients with cocaine abuse showed a consistent increase from year 2006 to 2018 with p <0.001. Conclusions: There is a recent uptrend in cocaine use among hospital admissions in the US from 2006 to 2018 with an increased rate of systemic manifestations. This highlights the impact of cocaine use on the health system and the dire need to address this growing problem.Item Using stimulants to treat ADHD-related emotional lability(Springer, 2014-10) Posner, Jonathan; Kass, Erica; Hulvershorn, Leslie; Department of Psychiatry, IU School of MedicineEmotional lability, or sudden strong shifts in emotion, commonly occurs in youth with attention-deficit/hyperactivity disorder. Although these symptoms are impairing and disruptive, relatively little research has addressed their treatment, likely due to the difficulty of reliable and valid assessment. Promising signals for symptom improvement have come from recent studies using stimulants in adults, children and adolescents. Similarly, neuroimaging studies have begun to identify neurobiological mechanisms underlying stimulants’ impact on emotion regulation capacities. Here, we review these recent clinical and neuroimaging findings, as well as neurocognitive models for emotional lability in ADHD, issues of relevance to prescribers and the important role of psychiatric comorbidity with treatment choices.