Nicole Mercado Fischer1, Jared T Hinkle2, Kate Perepezko1, Catherine C Bakker3, Meaghan Morris4, Martinus P G Broen5, Ankur Butala6, Ted M Dawson7, Albert F G Leentjens8, Zoltan Mari9, Cherie L Marvel6, Kelly A Mills10, Liana S Rosenthal10, Melissa D Shepard1, Alexander Pantelyat10, Arnold Bakker1, Olga Pletnikova11, Juan C Troncoso11, Jiangxia Wang12, Gregory M Pontone13. 1. Department of Psychiatry and Behavioral Sciences (NMF, JTH, KP, MDS, AB, GMP), Johns Hopkins School of Medicine, Baltimore, MD. 2. Department of Psychiatry and Behavioral Sciences (NMF, JTH, KP, MDS, AB, GMP), Johns Hopkins School of Medicine, Baltimore, MD; Medical Scientist Training Program (JTH), Johns Hopkins School of Medicine, Baltimore, MD. 3. Morris K. Udall Parkinson's Disease Research Center of Excellence (CCB, ZM, KAM, LSR, AP, JCT, GMP), Johns Hopkins School of Medicine, Baltimore, MD. 4. Clinical and Neuropathology Core (MM, OP, JCT), Johns Hopkins School of Medicine, Baltimore, MD. 5. Department of Neurology (MPGB), Maastricht University Medical Centre, Maastricht, the Netherlands. 6. Department of Neurology (AB, TMD, CLM, KAM, LSR, AP, GMP), Johns Hopkins School of Medicine, Baltimore MD. 7. Department of Neurology (AB, TMD, CLM, KAM, LSR, AP, GMP), Johns Hopkins School of Medicine, Baltimore MD; Neuroregeneration and Stem Cell Programs (TMD), Institute for Cell Engineering, Johns Hopkins School of Medicine, Baltimore, MD; Solomon H. Snyder Department of Neuroscience (TMD), Johns Hopkins School of Medicine, Baltimore, MD; Department of Pharmacology and Molecular Sciences (TMD), Johns Hopkins School of Medicine, Baltimore, MD. 8. Department of Psychiatry (AFGL), Maastricht University Medical Centre, Maastricht, The Netherlands. 9. Morris K. Udall Parkinson's Disease Research Center of Excellence (CCB, ZM, KAM, LSR, AP, JCT, GMP), Johns Hopkins School of Medicine, Baltimore, MD; Lou Ruvo Center for Brain Health (ZM), Cleveland Clinic, Las Vegas, NV. 10. Morris K. Udall Parkinson's Disease Research Center of Excellence (CCB, ZM, KAM, LSR, AP, JCT, GMP), Johns Hopkins School of Medicine, Baltimore, MD; Department of Neurology (AB, TMD, CLM, KAM, LSR, AP, GMP), Johns Hopkins School of Medicine, Baltimore MD. 11. Morris K. Udall Parkinson's Disease Research Center of Excellence (CCB, ZM, KAM, LSR, AP, JCT, GMP), Johns Hopkins School of Medicine, Baltimore, MD; Clinical and Neuropathology Core (MM, OP, JCT), Johns Hopkins School of Medicine, Baltimore, MD. 12. Department of Biostatistics (JW), Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 13. Department of Psychiatry and Behavioral Sciences (NMF, JTH, KP, MDS, AB, GMP), Johns Hopkins School of Medicine, Baltimore, MD; Morris K. Udall Parkinson's Disease Research Center of Excellence (CCB, ZM, KAM, LSR, AP, JCT, GMP), Johns Hopkins School of Medicine, Baltimore, MD; Department of Neurology (AB, TMD, CLM, KAM, LSR, AP, GMP), Johns Hopkins School of Medicine, Baltimore MD. Electronic address: gpontone@jhmi.edu.
Abstract
BACKGROUND: The pathological hallmarks of Parkinson's disease include intraneuronal Lewy bodies, neuronal loss, and gliosis. We aim to correlate Parkinson's disease neuropsychiatric symptoms, (e.g., depression, psychosis, and anxiety) with the severity of neuropathology in the substantia nigra and locus coeruleus. METHODS: The brains of 175 participants with a primary pathologic diagnosis of Parkinson's disease were analyzed semi-quantitatively to ascertain the burden of neuronal loss and gliosis and Lewy body pathology within the locus coeruleus and substantia nigra. Participants' history of anxiety, depression, and psychosis were determined using a chart-extracted medical history or record of formal psychiatric evaluation. RESULTS: Of the sample, 56% (n = 98), 50% (n = 88), and 31.25% (n = 55) of subjects had a diagnosis of psychosis, depression, and anxiety, respectively. Psychosis (χ2 = 7.1, p = 0.008, df = 1) and depression (χ2 = 7.2, p = 0.007, df = 1) were associated with severe neuronal loss and gliosis in the substantia nigra but not in the locus coeruleus. No association was observed between anxiety and neuronal loss and gliosis in either region. No neuropsychiatric symptoms were associated with Lewy body score. After controlling for disease duration and dementia, psychosis (odds ratio [OR]: 3.1, 95% confidence interval [CI]: 1.5-6.4, χ2 = 9.4, p = 0.012, df = 1) and depression (OR: 2.6, 95% CI: 1.3-5.0, χ2 = 7.9, p = 0.005, df = 1) remained associated with severe neuronal loss and gliosis in the substantia nigra. CONCLUSION: These results suggest that psychosis and depression in Parkinson's disease are associated with the underlying neurodegenerative process and demonstrate that cell loss and gliosis may be a better marker of neuropsychiatric symptoms than Lewy body pathology.
BACKGROUND: The pathological hallmarks of Parkinson's disease include intraneuronal Lewy bodies, neuronal loss, and gliosis. We aim to correlate Parkinson's disease neuropsychiatric symptoms, (e.g., depression, psychosis, and anxiety) with the severity of neuropathology in the substantia nigra and locus coeruleus. METHODS: The brains of 175 participants with a primary pathologic diagnosis of Parkinson's disease were analyzed semi-quantitatively to ascertain the burden of neuronal loss and gliosis and Lewy body pathology within the locus coeruleus and substantia nigra. Participants' history of anxiety, depression, and psychosis were determined using a chart-extracted medical history or record of formal psychiatric evaluation. RESULTS: Of the sample, 56% (n = 98), 50% (n = 88), and 31.25% (n = 55) of subjects had a diagnosis of psychosis, depression, and anxiety, respectively. Psychosis (χ2 = 7.1, p = 0.008, df = 1) and depression (χ2 = 7.2, p = 0.007, df = 1) were associated with severe neuronal loss and gliosis in the substantia nigra but not in the locus coeruleus. No association was observed between anxiety and neuronal loss and gliosis in either region. No neuropsychiatric symptoms were associated with Lewy body score. After controlling for disease duration and dementia, psychosis (odds ratio [OR]: 3.1, 95% confidence interval [CI]: 1.5-6.4, χ2 = 9.4, p = 0.012, df = 1) and depression (OR: 2.6, 95% CI: 1.3-5.0, χ2 = 7.9, p = 0.005, df = 1) remained associated with severe neuronal loss and gliosis in the substantia nigra. CONCLUSION: These results suggest that psychosis and depression in Parkinson's disease are associated with the underlying neurodegenerative process and demonstrate that cell loss and gliosis may be a better marker of neuropsychiatric symptoms than Lewy body pathology.
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