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5 - Biological Changes in Older People with Schizophrenia

from Section 2 - Biological, Neurocognitive, and Medical Aspects

Published online by Cambridge University Press:  15 March 2019

By
Michael B. Centorino  and
Susan K. Schultz
Edited by
Carl I. Cohen  and
Paul D. Meesters
Carl I. Cohen
Affiliation:
SUNY Downstate Medical Center
Paul D. Meesters
Affiliation:
Friesland Mental Health Services
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Summary

Age-related biological changes in schizophrenia are of great interest as a growing number of individuals with chronic mental illness are now reaching the age where medical comorbidities and neurodegenerative changes become more likely. Dramatic changes have occurred in the range and types of antipsychotic medications available, which has resulted in some benefits for older persons with schizophrenia as well as some new challenges in chronic treatment. This chapter will review findings from neuroimaging studies that have examined brain morphology, as well as functional imaging changes with age in persons with schizophrenia. It will also discuss advances in the understanding of the genetics of cognitive aging in schizophrenia and related biomarkers. The biologic effects of long-term use of antipsychotic medications in terms of dopamine reception function and movement disorders, as well as the effect on the development of the metabolic syndrome with age will be discussed.
Type
Chapter
Information
Schizophrenia and Psychoses in Later Life
New Perspectives on Treatment, Research, and Policy
 , pp. 55 - 68
Publisher: Cambridge University Press
Print publication year: 2019

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References

Johnstone, E.C., Frith, C.D., Crow, T.J., Husband, J., Kreel, L.. Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet 308: 924–6, 1976.CrossRefGoogle Scholar
Weinberger, D.R., Torrey, E.F., Neophytides, A.N.. Lateral cerebral ventricular enlargement in chronic schizophrenia. Arch Gen Psychiatry 36: 735–39, 1979.CrossRefGoogle ScholarPubMed
Pearlson, G.D., Garbacz, D.J., Tompkins, R.H., et al. Lateral cerebral ventrical size in late onset schizophrenia. In Schizophrenia and Aging, ed. Miller, N. E., Cohen, G.D. New York: Guilford: 246–248, 1987.Google Scholar
De Leon, M.J., Ferris, S.H., George, A.E., et al. Computed tomography evaluations of brain-behavior relationships in senile dementia of the Alzheimer's type. Neurobiol Aging 1: 69–79, 1980.CrossRefGoogle ScholarPubMed
Naeser, M.A., Gebhardt, C., Levine, H.L.. Decreased computerized tomography numbers in patients with presenile dementia: detection in patients with otherwise normal scans. Arch Neurol 37: 401–9, 1980.CrossRefGoogle ScholarPubMed
Veroff, A.E., Pearlson, G.D., Ahn, H.S.. CT scan and neuropsychological correlates of Alzheimer's disease and Huntington's disease. Brain Cogn 1(2): 177–84, 1982.CrossRefGoogle ScholarPubMed
Seno, H., Shibata, M., Fujimoto, A., et al. Computed tomographic study of aged schizophrenic patients. Psychiatry Clin Neurosci 51(6): 373–7, 1997.CrossRefGoogle ScholarPubMed
Putnam, K.M., Harvey, P.D.. Cognitive impairment and enduring negative symptoms: a comparative study of geriatric and nongeriatric schizophrenia patients. Schizophr Bull 26(4): 867–78, 2000.CrossRefGoogle ScholarPubMed
Harvey, M.P., Moriarty, P.J., Friedman, J.I., et al. Differential preservation of cognitive functions in geriatric patients with lifelong chronic schizophrenia: less impairment in reading compared with other skill areas. Biol Psychiatry 47(11): 962–8, 2000.CrossRefGoogle ScholarPubMed
Rossi, A., Bustini, M., Prosperini, P., et al. Neuromorphological abnormalities in schizophrenic patients with good and poor outcome. Acta Psychiatr Scand 101(2): 161–6, 2000.CrossRefGoogle ScholarPubMed
Tandon, R., DeQuardo, J.R., Taylor, S.F., et al. Phasic and enduring negative symptoms in schizophrenia: biological markers and relationship to outcome. Schizophr Res 45(3): 191–201, 2000.CrossRefGoogle ScholarPubMed
Mathalon, D.H., Sullivan, E.V., Lim, K.O., Pfefferbaum, A.. Progressive brain volume changes and the clinical course of schizophrenia in men: a longitudinal magnetic resonance imaging study. Arch Gen Psychiatry 58(2): 148–57, 2001.CrossRefGoogle Scholar
Pearlson, G.D., Marsh, L.. Structural brain imaging in schizophrenia: a selective review. Biol Psychiatry 46: 627–49, 1999.CrossRefGoogle ScholarPubMed
Keshavan, M.S., Mulsant, B.H., Sweet, R.A., et al. MRI changes in schizophrenia in late life: a preliminary controlled study. Psych Res 60: 117–23, 1996.CrossRefGoogle ScholarPubMed
Koutsouleris, N., Davatzikos, C., Borgwardt, S., et al. Accelerated brain aging in schizophrenia and beyond: a neuroanatomical marker of psychiatric disorders. Schizophr Bull 40(5): 1140–53, 2014.CrossRefGoogle ScholarPubMed
Cropley, V.L., Klauser, P., Lenroot, R.K., et al. Accelerated gray and white matter deterioration with age in schizophrenia. Am J Psychiatry 174(3): 286–295, 2017.CrossRefGoogle ScholarPubMed
Andreasen, N.C., Rezai, K., Alliger, R., et al. Hypofrontality in neuroleptic naïve patients and in patients with chronic schizophrenia: assessment with xenon 133 single-photon emission computed tomography and the Tower of London. Arch Gen Psychiatry 49(12): 943–58, 1992.CrossRefGoogle ScholarPubMed
Buchsbaum, M.S., Hazlett, E.A.. Functional brain imaging and aging in schizophrenia. Schizophr Res 27(2-3): 129–41, 1997.CrossRefGoogle ScholarPubMed
Goldstein, P.C., Brown, G.G., Marcus, A., Ewing, J.R.. Effects of age, neuropsychological impairment and medication on regional cerebral blood flow in schizophrenia and major affective disorder. Henry Ford Hosp Med J 38(4): 202–6, 1990.Google ScholarPubMed
Dupont, L.P., Lehr, P.P., Lamoureaux, G., et al. Preliminary report: cerebral blood flow abnormalities in older schizophrenic patients. Psychiatry Res 55(3): 121–30, 1994.CrossRefGoogle ScholarPubMed
Harvey, P.D., Lombardi, J., Leibman, M., et al. Cognitive impairment and negative symptoms in geriatric chronic schizophrenia patients: a follow-up study. Schizophr Res (22): 223–31, 1996.CrossRefGoogle ScholarPubMed
Sheffield, J.M., Repovs, G., Harms, M.P., et al. Evidence for accelerated decline of functional brain network efficiency in schizophrenia. Schizophr Bull 42(3): 753–61, 2015.Google ScholarPubMed
Snitz, B.E., Macdonald, A.W., Carter, C.S.. Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophr Bull 32(1): 179–94, 2006.Google ScholarPubMed
Fallon, S.J., Williams-Gray, C.H., Barker, R.A., Owen, A.M., Hampshire, A.. Prefrontal dopamine levels determine the balance between cognitive stability and flexibility. Cerebral Cortex 23(2): 361–9, 2013.CrossRefGoogle ScholarPubMed
Ira, E., Zanoni, M., Ruggeri, M., Dazzan, P., Tosato, S.. COMT, neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation. J Psychiatry Neurosci 38(6): 366–80, 2013.CrossRefGoogle ScholarPubMed
Niizato, K., Genda, K., Nakamura, R., Iritani, S., Ikeda, K.. Cognitive decline in schizophrenics with Alzheimer's disease: a mini-review of neuropsychological and neuropathological studies. Prog Neuro-Psychopharmacol Biol Psychiatry 25(7): 1359–66, 2001.CrossRefGoogle ScholarPubMed
Thabit, H., Kennelly, S.M., Bhagarva, A., et al. Utilization of Frontal Assessment Battery and Executive Interview 25 in assessing for dysexecutive syndrome and its association with diabetes self-care in elderly patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 86(3): 208–12, 2009.CrossRefGoogle ScholarPubMed
Joober, R., Rouleau, G., Fon, E., et al. Apolipoprotein E genotype in schizophrenia. Am J Med Genet 67(2): 235, 1996.CrossRefGoogle ScholarPubMed
Liebers, D.T., Pirooznia, M., Seiffudin, F., et al. Polygenic risk of schizophrenia and cognition in a population-based survey of older adults. Schizophr Bull 42(4): 984–91, 2016.CrossRefGoogle Scholar
Mullins, N., Perroud, N., Uher, R., et al. Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: a genome-wide association and polygenic scoring study. Am J Med Genet B, Neuropsychiatric Genet 165B(5): 428–37, 2014.Google ScholarPubMed
Joseph, J., Depp, C., Martin, A.S., et al. Associations of high sensitivity C-reactive protein levels in schizophrenia and comparison groups. Schizophr Res 168(1–2): 456–60, 2015.CrossRefGoogle ScholarPubMed
Osler, M., Rostrup, E., Nordentoft, M., et al. Influence of early life characteristics on psychiatric admissions and impact of psychiatric disease on inflammatory biomarkers and survival: a Danish cohort study. World Psychiatry 14(3): 364–5, 2015.CrossRefGoogle ScholarPubMed
Lee, E.E., Hong, S., Martin, A.S., Eyler, L.T., Jeste, D.V.. Inflammation in schizophrenia: cytokine levels and their relationships to demographic and clinical variables. Am J Geriatr Psychiatry 25(1): 50–61, 2017.CrossRefGoogle ScholarPubMed
Czepielewski, L.S., Massuda, R., Panizzutti, B., et al. Telomere length and CCL11 levels are associated with gray matter volume and episodic memory performance in schizophrenia: evidence of pathological accelerated aging. Schizophr Bull 44(1): 158–67, 2018.CrossRefGoogle ScholarPubMed
Czepielewski, L.S., MassudaMassuda, R.R., Panizzutti, B.B., et al. Telomere length in subjects with schizophrenia, their unaffected siblings and healthy controls: evidence of accelerated aging. Schizophr Res 174(1–3): 39–42, 2016.CrossRefGoogle ScholarPubMed
Clementz, B.A., Sweeney, J.A., Hamm, J.P., et al. Identification of distinct psychosis biotypes using brain-based biomarkers. Am J Psychiatry 173(4): 373–84, 2016.CrossRefGoogle ScholarPubMed
Arnold, S.E., Trojanowski, J.Q., Gur, R.E., et al. Absence of neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia. Arch Gen Psychiatry 55(3): 225–32, 1998.CrossRefGoogle Scholar
Arnold, S.E., Trojanowski, J.Q.. Cognitive impairment in elderly schizophrenia: a dementia (still) lacking distinctive histopathology. Schizophr Bull 22(1): 5–9, 1996.CrossRefGoogle ScholarPubMed
Baldessarini, R.J., Hegarty, J.D., Bird, E.D., Benes, F.M.. Meta-analysis of postmortem studies of Alzheimer's disease-like neuropathology in schizophrenia. Am J Psychiatry 154(6): 861–3, 1997.Google ScholarPubMed
Dwork, A.J., Susser, E.S., Keilp, J., et al. Senile degeneration and cognitive impairment in chronic schizophrenia. Am J Psychiatry 155(11): 1536–43, 1998.CrossRefGoogle ScholarPubMed
Radewicz, K., Garey, L.J., Gentleman, S.M., et al. Increase in HLA-DR immunoreactive microglia in frontal and temporal cortex of chronic schizophrenics. J Neuropathol Exp Neurol 59(2): 137–50, 2000.CrossRefGoogle ScholarPubMed
Najjar, S., Pearlman, D.M.. Neuroinflammation and white matter pathology in schizophrenia: systematic review. Schizophr Res 161(1): 102–12, 2015.CrossRefGoogle ScholarPubMed
Volk, D.W. Role of microglia disturbances and immune-related marker abnormalities in cortical circuitry dysfunction in schizophrenia. Neurobiol Dis 99: 58–65, 2017.CrossRefGoogle ScholarPubMed
Laskaris, L.E., Di Biase, M.A., Everall, I., et al. Microglial activation and progressive brain changes in schizophrenia. Br J Pharmacol 173(4): 666–80, 2016.CrossRefGoogle ScholarPubMed
Bakhshi, K., Chance, S.A.. The neuropathology of schizophrenia: a selective review of past studies and emerging themes in brain structure and cytoarchitecture. Neuroscience 303: 82–102, 2015.CrossRefGoogle ScholarPubMed
Obuchowicz Bielecka-Wajdman, A.M., Paul-Samojedny, M., Nowacka, M.. Different influence of antipsychotics on the balance between pro- and anti-inflammatory cytokines depends on glia activation: an in vitro study. Cytokine 94: 37–44, 2017.CrossRefGoogle Scholar
Lieberman, J.A., Stroup, T.S., McEvoy, J.P., et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353(12): 1209–23, 2005.CrossRefGoogle ScholarPubMed
Jones, P.B., Barnes, T.R., Davies, L., et al. Randomized controlled trial of the effect on quality of life of second- vs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 63(10): 1079–87, 2006.CrossRefGoogle Scholar
Lerner, P.P., Miodownik, C., Lerner, V.. Tardive dyskinesia (syndrome): current concept and modern approaches to its management. Psychiatry Clin Neurosci 69(6): 321–34, 2015.CrossRefGoogle ScholarPubMed
Gerlach, J. Prevention/treatment of tardive dyskinesia. Acta Psychiatr Scand Suppl 291: 117–28, 1981.Google ScholarPubMed
Lencz, T., Malhotra, A.K.. Pharmacogenetics of antipsychotic-induced side effects. Dialogues Clin Neurosci 11(4): 405–15, 2009.CrossRefGoogle ScholarPubMed
Woerner, M.G., Correll, C.U., Alvir, J.M., et al. Incidence of tardive dyskinesia with risperidone or olanzapine in the elderly: results from a 2-year, prospective study in antipsychotic-naïve patients. Neuropsychopharmacology 36(8): 1738–46, 2011.CrossRefGoogle ScholarPubMed
Woerner, M.G., Alvir, J.M., Saltz, B.L., et al. Prospective study of tardive dyskinesia in the elderly: rates and risk factors. Am J Psychiatry 155(11): 1521–8, 1998.CrossRefGoogle ScholarPubMed
Jeste, D.V., Caligiuri, M.P., Paulsen, J.S., et al. Risk of tardive dyskinesia in older patients: a prospective longitudinal study of 266 outpatients. Arch Gen Psychiatry 52(9): 756–65, 1995.CrossRefGoogle ScholarPubMed
Lee, P.E., Sykora, K., Gill, S.S., et al. Antipsychotic medications and drug-induced movement disorders other than parkinsonism: a population-based cohort study in older adults. J Am Geriatr Soc 53(8): 1374–9, 2005.CrossRefGoogle ScholarPubMed
Woerner, M.G., Correll, C.U., Alvir, J.M., et al. Incidence of tardive dyskinesia with risperidone or olanzapine in the elderly: results from a 2-year, prospective study in antipsychotic-naïve patients. Neuropsychopharmacology 36(8): 1738–46, 2011.CrossRefGoogle ScholarPubMed
Kinon, B.J., Kollack-Walker, S., Jeste, D., et al. Incidence of tardive dyskinesia in older adult patients treated with olanzapine or conventional antipsychotics. J Geriatr Psychiatry Neurol 28(1): 67–79, 2015.CrossRefGoogle ScholarPubMed
O'Brien, A. Comparing the risk of tardive dyskinesia in older adults with first-generation and second-generation antipsychotics: a systematic review and meta-analysis. Int J Geriatr Psychiatry 31(7): 683–93, 2016.CrossRefGoogle ScholarPubMed
Byne, W., Stamu, C., White, L., et al. Prevalence and correlates of parkinsonism in an institutionalized population of geriatric patients with chronic schizophrenia. Int J Geriatr Psychiatry 15(1): 7–13, 2000.3.0.CO;2-Z>CrossRefGoogle Scholar
Dubovsky, S.I., Dubovsky, A.N.. Geriatric neuropsychopharmacology. In Textbook of Geriatric Neuropsychiatry, ed. Dubovsky, S.L., Buzan, R., Washington DC: The American Psychiatric Press: 800–1, 2000.Google Scholar
Volkow, N.D., Logan, J., Fowler, J.S., et al. Association between age-related decline in brain dopamine activity and impairment in frontal and cingulate metabolism. Am J Psychiatry 157: 75–80, 2000.CrossRefGoogle ScholarPubMed
Seeman, P., Tinazzi, M.. Loss of dopamine neuron terminals in antipsychotic-treated schizophrenia; relation to tardive dyskinesia. Prog Neuropsychopharmacol Biol Psychiatry 44: 178–83, 2013.CrossRefGoogle ScholarPubMed
Miller, D.D., Andreasen, N.C., O'Leary, D.S., et al. Effect of antipsychotics on regional cerebral blood flow measured with positron emission tomography. Neuropsychopharmacology 17(4): 230–40, 1997.CrossRefGoogle ScholarPubMed
Gur, R.E., Maany, V., Mozley, P.D., et al. Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. Am J Psychiatry 155(12): 1711–17, 1998.CrossRefGoogle ScholarPubMed
Corson, P.W., Nopoulos, P., Miller, D.D., Arndt, S., Andreasen, N.C.. Change in basal ganglia volume over 2 years in patients with schizophrenia: typical versus atypical neuroleptics. Am J Psychiatry 156(8): 1200–4, 1999.CrossRefGoogle ScholarPubMed
Lang, D.J., Kopala, L.C., Vandorpe, R.A., et al. An MRI study of basal ganglia volumes in first-episode schizophrenia patients treated with risperidone. Am J Psychiatry 158(4): 625–31, 2001.CrossRefGoogle ScholarPubMed
Hauser, R.A., Factor, S.A., Marder, S.R., et al. KINECT 3: a phase 3 randomized, double-blind, placebo-controlled trial of valbenazine for tardive dyskinesia. Am J Psychiatry 174(5): 476–84, 2017.CrossRefGoogle ScholarPubMed
Kenney, C., Hunter, C., Jankovic, J.. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord 22(2): 193–7, 2007.CrossRefGoogle ScholarPubMed
Lett, T.A., Wallace, T.J., Chowdhury, N.I., et al. Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications. Mol Psychiatry 17(3): 242–66, 2012.CrossRefGoogle ScholarPubMed
Mitchell, A.J., Vancampfort, D., Sweers, K., et al. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders: a systematic review and meta-analysis. Schizophr Bull 39(2): 306–18, 2013.Google ScholarPubMed
Jin, H., Folsom, D., Sasaki, A., et al. Increased Framingham 10-year risk of coronary heart disease in middle-aged and older patients with psychotic symptoms. Schizophr Res 125(2–3): 295–9, 2011.CrossRefGoogle ScholarPubMed
Guillemot-Legris, O., Muccioli, G.G.. Obesity-induced neuroinflammation: beyond the hypothalamus. Trends Neurosci 40(4): 237–53, 2017.CrossRefGoogle ScholarPubMed
Gohlke, J.M., Dhurandhar, E.J., Correll, C.U., et al. Recent advances in understanding and mitigating adipogenic and metabolic effects of antipsychotic drugs. Front Psychiatry 28(3): 62, 2012.Google Scholar

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