Browsing by Subject "Dual diagnosis"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Cortical–striatal gene expression in neonatal hippocampal lesion (NVHL)-amplified cocaine sensitization
    (Wiley, 2013) Chambers, R. A.; McClintick, J. N.; Sentir, A. M.; Berg, S. A.; Runyan, M.; Choi, K. H.; Edenberg, H. J.; Biochemistry and Molecular Biology, School of Medicine
    Cortical-striatal circuit dysfunction in mental illness may enhance addiction vulnerability. Neonatal ventral hippocampal lesions (NVHL) model this dual diagnosis causality by producing a schizophrenia syndrome with enhanced responsiveness to addictive drugs. Rat genome-wide microarrays containing >24 000 probesets were used to examine separate and co-occurring effects of NVHLs and cocaine sensitization (15 mg/kg/day × 5 days) on gene expression within medial prefrontal cortex (MPFC), nucleus accumbens (NAC), and caudate-putamen (CAPU). Two weeks after NVHLs robustly amplified cocaine behavioral sensitization, brains were harvested for genes of interest defined as those altered at P < 0.001 by NVHL or cocaine effects or interactions. Among 135 genes so impacted, NVHLs altered twofold more than cocaine, with half of all changes in the NAC. Although no genes were changed in the same direction by both NVHL and cocaine history, the anatomy and directionality of significant changes suggested synergy on the neural circuit level generative of compounded behavioral phenotypes: NVHL predominantly downregulated expression in MPFC and NAC while NVHL and cocaine history mostly upregulated CAPU expression. From 75 named genes altered by NVHL or cocaine, 27 had expression levels that correlated significantly with degree of behavioral sensitization, including 11 downregulated by NVHL in MPFC/NAC, and 10 upregulated by NVHL or cocaine in CAPU. These findings suggest that structural and functional impoverishment of prefrontal-cortical-accumbens circuits in mental illness is associated with abnormal striatal plasticity compounding with that in addictive disease. Polygenetic interactions impacting neuronal signaling and morphology within these networks likely contribute to addiction vulnerability in mental illness.
  • Thumbnail Image
    Item
    Criminal Offending and Incarceration in United States Adults With Early Phase Psychosis and Comorbid Substance Use Disorder
    (Wiley, 2025) Webster, Kyle D.; Gunter, Tracy D.; Vohs, Jenifer L.; Breier, Alan; Psychiatry, School of Medicine
    Aim: Studies have shown that people experiencing early phase psychosis (EPP) are at increased risk for criminal conviction and incarceration. However, there is limited data looking at overall legal burden. To address these gaps in the literature, the goal of this study was to categorise criminal charges and convictions using the United States Federal Bureau of Investigation (FBI) uniform crime reporting (UCR) program, assess frequency of incarcerations, and describe the frequency of substance use disorder (SUD) diagnoses and its relationship to criminal offending and incarceration in a well categorised EPP population. Methods: A sample of 309 adults experiencing EPP were enrolled in a specialty care clinic. The research team expanded upon prior work and collected data from three public databases to identify legal burden in this population. Results: Almost 50% (n = 155) of subjects had a history of a criminal charge, 34% (n = 104) of subjects had a history of criminal conviction, and 40% (n = 123) of subjects had at least one incarceration event. The most common typology of criminal offence were crimes against society. Lastly, a dual diagnosis was statistically associated with incarcerations (χ2 = 10.152, p < 0.0011), crimes against society (χ2 = 13.172, p < 0.0002), and crimes against persons (χ2 = 9.136, p < 0.0023). Conclusions: These data highlight the high legal burden people experiencing EPP face and the need for future work to examine the risks incarceration places on this population. This work also shows the need for specialty care clinics managing EPP to be proficient in treating a dual diagnosis or the need to partner with an appropriate clinic.
  • Thumbnail Image
    Item
    Integrated Effects of Neonatal Ventral Hippocampal Lesions and Impoverished Social-Environmental Rearing on Endophenotypes of Mental Illness and Addiction Vulnerability
    (Karger, 2019) Chambers, Robert Andrew; Sentir, Alena M.; Psychiatry, School of Medicine
    A wide range of mental illnesses show high rates of addiction comorbidities regardless of their genetic, neurodevelopmental, and/or adverse-environmental etiologies. Understanding how the spectrum of mental illnesses produce addiction vulnerability will be key to discovering more effective preventions and integrated treatments for adults with addiction and dual diagnosis comorbidities. A population of 131 rats containing a spectrum of etiological mental illness models and degrees of severity was experimentally generated by crossing neonatal ventral hippocampal lesions (NVHL; n = 68) or controls (SHAM-operated; n = 63) with adolescent rearing in environmentally/socially enriched (ENR; n = 66) or impoverished (IMP; n = 65) conditions. This population was divided into 2 experiments: first, examining NVHL and IMP effects on novelty and mild stress-induced locomotion across 3 adolescent ages; second, looking at initial cocaine reactivity and long-term cocaine behavioral sensitization in adulthood. NVHL and IMP-environmental conditions independently produced remarkably similar and robustly significant abnormalities of hyperreactivity to novelty, mild stress, and long-term cocaine sensitization. The combined NVHL-IMP groups showed the most severe phenotypes across the board, so that the mental illness and addiction vulnerability phenotypes increased together in severity in a consistent stepwise progression from the healthiest rats to those with the greatest loading of etiological models. These findings add weight to our understanding of mental illness and addiction vulnerability as brain disorders that are biologically and developmentally unified in ways that transcend etiological causes, and yet co-intensify with increased loading of etiological conditions. Combining neurodevelopmental and adverse-environmental models of mental illness may provide an approach to identifying and therapeutically targeting cortical-striatal-limbic network mechanisms that generate addiction and dual diagnosis diseases.
  • Thumbnail Image
    Item
    Psychiatric Co-Morbidities in Pregnant Women with Opioid Use Disorders: Prevalence, Impact, and Implications for Treatment
    (Springer, 2017) Arnaudo, Camila L.; Andraka-Christou, Barbara; Allgood, Kacy; Department of Psychiatry, IU School of Medicine
    Purpose of Review This review seeks to investigate three questions: What is the prevalence of comorbid psychiatric diagnoses among pregnant women with opioid use disorder (OUD)? How do comorbid psychiatric illnesses impact pregnant women with OUD? And how do comorbid psychiatric illnesses affect the ability of pregnant women with OUD to adhere to and complete OUD treatment? Recent Findings Based on this literature review, 25–33% of pregnant women with OUD have a psychiatric comorbidity, with depression and anxiety being especially common. However, of the 17 studies reviewed only 5 have prevalence rates of dual diagnosis in pregnant women with OUD as their primary outcome measures, their N’s were typically small, methods for determining psychiatric diagnosis were variable, and many of the studies were undertaken with women presenting for treatment which carries with its implicit selection bias. Of the women enrolled in treatment programs for SUD, those with psychiatric comorbidity were more likely to have impaired psychological and family/social functioning than those without psychiatric comorbidity. Greater severity of comorbid psychiatric illness appears to predict poorer adherence to treatment, but more research is needed to clarify this relationship with the psychiatric illness is less severe. Summary While cooccurrence of psychiatric disorders in pregnant women with opioid use disorder appears to be common, large population-based studies with validated diagnostic tools and longitudinal assessments are needed to obtain definitive rates and characteristics of cooccurring illnesses. Integrated prenatal, addiction, and psychiatric treatment in a setting that provides social support to pregnant patients with OUD is most effective in maintaining women in treatment. More research is still needed to identify optimal treatment settings, therapy modalities, and medication management for dually diagnosed pregnant women with OUD.
  • Thumbnail Image
    Item
    Toward early estimation and treatment of addiction vulnerability: radial arm maze and N-acetyl cysteine before cocaine sensitization or nicotine self-administration in neonatal ventral hippocampal lesion rats
    (Springer-Verlag, 2016-12) Rao, Kalyan N.; Sentir, Alena M.; Engleman, Eric A.; Bell, Richard L.; Hulvershorn, Leslie A.; Breier, Alan; Chambers, R. Andrew; Department of Psychiatry, IU School of Medicine
    RATIONAL: Prefrontal cortical (PFC)-hippocampal-striatal circuits, interconnected via glutamatergic signaling, are dysfunctional in mental illnesses that involve addiction vulnerability. OBJECTIVES: In healthy and neurodevelopmentally altered rats, we examined how Radial Arm Maze (RAM) performance estimates addiction vulnerability, and how starting a glutamatergic modulating agent, N-acetyl cysteine (NAC) in adolescence alters adult mental illness and/or addiction phenotypes. METHODS: Rats with neonatal ventral hippocampal lesions (NVHL) vs. SHAM-operated controls were randomized to NAC vs. saline in adolescence followed by cognitive testing (RAM) in early adulthood and then cocaine behavioral sensitization (experiment 1; n = 80) or nicotine self-administration (experiment 2; n = 12). RESULTS: In experiment 1, NVHL rats showed over-consumption of food (Froot-Loops (FL)) baiting the RAM with poor working memory (low-arm entries to repeat (ETR)), producing an elevated FL to ETR ratio ("FLETR"; p < 0.001). FLETR was the best linear estimator (compared to FL or ETR) of magnitude of long-term cocaine sensitization (R (2) = 0.14, p < 0.001). NAC treatment did not alter FL, ETR, FLETR, or cocaine sensitization. In experiment 2, FLETR also significantly and uniquely correlated with subsequent drug seeking during nicotine-induced reinstatement after extinction of nicotine self-administration (R (2) = 0.47, p < 0.01). NAC did not alter RAM performance, but significantly reversed NVHL-induced increases in nicotine seeking during extinction and reinstatement. CONCLUSIONS: These findings demonstrate the utility of animal models of mental illness with addiction vulnerability for developing novel diagnostic measures of PFC-hippocampal-striatal circuit dysfunction that may reflect addiction risk. Such tests may direct pharmacological treatments prior to adulthood and addictive drug exposure, to prevent or treat adult addictions.
  • Thumbnail Image
    Item
    Ventral and dorsal striatal dopamine efflux and behavior in rats with simple vs. co-morbid histories of cocaine sensitization and neonatal ventral hippocampal lesions
    (Springer Verlag, 2010-07-15) Chambers, Robert Andrew; Sentir, Alena M.; Engleman, Eric A.; Psychiatry, School of Medicine
    xposing animal models of mental illness to addictive drugs provides an approach to understanding the neural etiology of dual diagnosis disorders. Previous studies have shown that neonatal ventral hippocampal lesions (NVHL) in rats produce features of both schizophrenia and addiction vulnerability. Objective This study investigated ventral and dorsal striatal dopamine (DA) efflux in NVHL rats combined with behavioral sensitization to cocaine. Methods Adult NVHL vs. SHAM-operated rats underwent a 5-day injection series of cocaine (15 mg/kg/day) vs. saline. One week later, rats were cannulated in nucleus accumbens SHELL, CORE, or caudate–putamen. Another week later, in vivo microdialysis sampled DA during locomotor testing in which a single cocaine injection (15 mg/kg) was delivered. Results NVHLs and cocaine history significantly increased behavioral activation approximately 2-fold over SHAM-saline history rats. DA efflux curves corresponded time dependently with the cocaine injection and locomotor curves and varied significantly by striatal region: Baseline DA levels increased 5-fold while cocaine-stimulated DA efflux decreased by half across a ventral to dorsal striatal gradient. However, NVHLs, prior cocaine history, and individual differences in behavior were not underpinned by differential DA efflux overall or within any striatal region.Conclusion Differences in ventral/dorsal striatal DA efflux are not present in and are not required for producing differential levels of acute cocaine-induced behavioral activation in NVHLs with and without a behaviorally sensitizing cocaine history. These findings suggest other neurotransmitter systems, and alterations in striatal network function post-synaptic to DA transmission are more important to understanding the interactive effects of addictive drugs and mental illness.