The nosology, classification, and biological basis of psychosis in the elderly have been much debated. Psychotic features are seen in schizophrenia, affective illness, and dementia in the elderly. This article reviews evidence for the biological basis of psychosis in older people. In schizophrenia, there is evidence of gender differences in brain volume loss and dopamine receptor numbers, possibly linked to estrogen loss in women. Neuroimaging evidence of ventricular brain changes and more dopamine receptors have also been documented. In Alzheimer’s disease, genetic factors such as PS1 and ApoE4 have been associated with psychotic symptoms, and histopathological studies have revealed differences in neuronal pathology. Radiological studies have shown right and left hemisphere differences in size, blood flow, and glucose metabolism between psychotic and nonpsychotic patients. In affective illnesses, there is evidence of structural brain changes in psychotic depression. Ample evidence suggests that biological substrates underlie many psychotic symptoms. More research will identify causal links between brain changes, symptom appearance, and the effects of psychosocial factors in their genesis.
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References
1.
1. Hamilton M, ed. Fish’s clinical psychopathology: signs and symptoms in psychiatry. 2nd ed. Bristol, UK: Wright, 1985:11-12.
2.
2. Berrios BE. Late onset mental disorders: a conceptual history. In: Late-onset mental disorders: the Potsdam conference. Glasgow, UK: Bell & Bain, 1999:1-23.
3.
3. Lisa T, Zorrilla E, Jeste D. Late-life psychotic disorders: nosology and classification. In: Copeland JRM, Abou-Saleh MT, BlazerD, eds. Principles and practice of geriatric psychiatry. 2nd ed. Chichester, UK: John Wiley, 2002:493-496.
4.
4. Bleuler M. Late schizophrenic clinical pictures. Fortschr Neurol Psychiatr1943; 15:259-290.
5.
5. Roth M, Morrissey JD. Problems in the diagnosis and classification of mental disorders in old age. J Mental Sci1952; 98:66-80.
6.
6. Andreasen NC. I don’t believe in late onset schizophrenia. In: Howard R, Rabins PV, Castle DJ, eds. Late-onset schizophrenia. Petersfield, UK: Wrightson Biomedical, 1999:111-113.
7.
7. Howard R. Schizophrenia-like psychosis with onset in late life. In: Howard R, Rabins PV, Castle DJ, eds. Late-onset schizophrenia. Petersfield, UK: Wrightson Biomedical, 1999:127-138.
8.
8. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994.
9.
9. Robbins TW, Sahakian B. Computer methods of assessment of cognitive function. In: Copeland JRM, Abou-Saleh MT, Blazer D, eds. Principles and practice of geriatric psychiatry. 2nd ed. Chichester, UK: John Wiley, 2002:147-151.
10.
10. Murphy DGM, DeCarli C, McIntosh AR, et al. Sex differences in human brain morphometry and metabolism: an in-vivo quantitative magnetic resonance imaging and positron emission tomography study on the effect of aging. Arch Gen Psychiatry1996; 53:585-594.
11.
11. Pohjalainen T, Rinne JO, Nagren K, et al. Sex differences in the striatal dopamine D2 receptor binding characteristics in vivo. Am J Psychiatry1998; 155:768-773.
12.
12. Volkow ND, Gur RC, Wang G, et al. Association between decline in brain dopamine activity with age and cognitive and motor impairment in health individuals. Am J Psychiatry1998; 155:344-349.
13.
13. Seeman MV. Gender differences in schizophrenia. Can J Psychiatry1982; 27:107-111.
14.
14. Burns A, Carrick J, Ames D, et al. The cerebral cortical appearance in late paraphrenia. Int J Geriatr Psychiatry1989; 4:31-34.
15.
15. Howard RJ, Forstl H, Almeida O, et al. Computer-assisted CT measurements in late paraphrenics with and without Schneiderian first-rank symptoms: a preliminary report. Int J Geriatr Psychiatry1992; 7:35-38.
16.
16. Howard RJ, Forstl H, Almeida O, et al. First-rank symptoms of Schneider in late paraphrenia: cortical structural correlates. Br J Psychiatry1992; 160:108-109.
17.
17. Pearlson G, Tune L, Wong D, et al. Quantitative D2 dopamine receptor PET and structural MRI changes in late onset schizophrenia. Schizophr Bull1993; 19:783-795.
18.
18. Miller BL, Lesser IM, Boone KB, et al. Brain lesions and cognitive function in late-life psychosis. Br J Psychiatry1991; 158:76-82.
19.
19. Krull AJ, Press G, Dupont R, et al. Brain imaging in late-onset schizophrenia and related psychoses. Int J Geriatr Psychiatry1991; 6:651-658.
20.
20. Burns A, Carrick J, Ames D, et al. The cerebral cortical appearance in late paraphrenia. Int J Geriatr Psychiatry1988; 12:712-717.
21.
21. Wong D, Wagner HJ, Dannals R, et al. Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science1984; 31:1393-1396.
22.
22. Wong D, Pearlson G, Tune L, et al. Quantification of neuroreceptors in the living human brain: IV. Effect of ageing and elevations of D2 like receptors in schizophrenia and bipolar illnesses. Cereb Blood Flow Metab1997; 17:331-342.
23.
23. Pearlson G. Brain imaging studies in late onset schizophrenia. In: Howard R, Rabins PV, Castle DJ, eds. Late-onset schizophrenia. Petersfield, UK: Wrightson Biomedical, 1999:191-204.
24.
24. Tariot PN. The Behaviour Rating Scale for Dementia. Am J Psychiatry1995; 152:1349-1357.
25.
25. Harvey RJ, Ellison D, Hardy J, et al. Chromosome 14 familial AD: the clinical and neuropathological characteristics of a family with a leucine-serine (L250S) substitution at codon 250 of the presenilin 1 gene. J Neurol Neurosurg Psychiatry1998; 64:44-49.
26.
26. Lehtovirta M, Soininen H, Helisalmi S, et al. Clinical and neuropsychological characteristics in familial and sporadic AD. Relation to apolipoprotein E polymorphism. Neurology1996; 49:794-797.
27.
27. Ballard C, Massey H, Lamb H, Morris C. Apolipoprotein E: noncognitive symptoms and cognitive decline in late-onset AD. J Neurol Neurosurg Psychiatry1997; 63:273-274.
28.
28. Holmes C, Arranz MJ, Powell JF, et al. 5-HT2A and 5-HT2C receptor polymorphisms and psychopathology in late onset AD. Hum Mol Genet1998; 7:1507-1509.
29.
29. Sweet RA, Nimgaonkar VL, Kamboh MI, et al. Dopamine receptor genetic variation, psychosis and aggression in AD. Arch Neurol1998; 55:1335-1340.
30.
30. Sweet RA, Nimgaonkar VL, Devlin B, Jeste DV. Psychotic symptoms in AD: evidence for a distinct phenotype. Mol Psychiatry2003; 8(4):383-392.
31.
31. Forstl H, Burns A, Levy R, Cairne N. Neuropathological correlates of psychotic phenomena in confirmed AD. Br J Psychiatry1994; 165:53-59.
32.
32. Zubenko GS, Moossy J, Martinez AJ, et al. Neruopathologic and neurochemical correlates of psychoses in primary dementia. Arch Neurol1991; 8:619-624.
33.
33. Bondaroff W. Neuropathology of psychotic symptoms in AD. Int Psychogeriatr1996; 8(suppl 3):233-237.
34.
34. Mukaetova-Ladinska EB, Harrington CR, Xueref J, et al. Biochemical, neuropathological, and clinical correlations of neurofibrillary degeneration in Alzheimer’s disease. In: Bergener M, Finkel S, eds. Treating Alzheimer’s and other dementias: clinical application of recent research advances. New York: Springer, 1995:57-80.
35.
35. Forstl H, Almeida O, Owen A, et al. Psychiatric, neurological and medical aspects of misidentification syndromes. Psychol Med1991; 21:1-6.
36.
36. Binetti G, Padovani A, Magni E, et al. Delusions and dementia: clinical and CT correlates. Acta Neurol Scand1995; 91:271-275.
37.
37. Kotrla KJ, Chacko RC, Harper RG, et al. SPECT findings on psychosis in AD. Am J Psychiatry1995; 152:1470-1475.
38.
38. Hirono N, Mori E, Ishii K, et al. Alteration of regional cerebral glucose utilization with delusions in AD. J Neuropsychiatry Clin Neurosci1998; 10:433-439.
39.
39. McKeith IG. Behavioral and psychological symptoms of dementia and dementia with Lewy bodies. Int Psychogeriatr2000; 12(suppl 1):189-193.
40.
40. McKeith IG. Dementia with Lewy bodies: clinical and pathological diagnosis. Alzheimer Rep1998; 1:83-87.
41.
41. Perry EK, Kerwin J, Perry RH, et al. Cerebral cholinergic activity is related to the incidence of visual hallucinations in senile dementia of Lewy body type. Dementia1990; 1:2-4.
44. Sweeny D, Nelson C, Bowers M, et al. Delusional vs. nondelusional depression—neurochemical differences. Lancet1978; 2:100-101.
45.
45. Maes MH, De Rutyer M, Suy E. Prediction of subtype and severity of depression by means of dexamethasone suppression test, L-tryptophan: competing amino acid ratio, and MHPG flow. Biol Psychiatry1987; 22:177-188.
46.
46. Edwards DJ, Spiker DG, Neil JF, et al. MHPG excretion in depression. Psychiatry Res1980; 2:295-305.
47.
47. Meltzer HY, Hyong WC, Caroll BJ, et al. Serum dopaminebhydrolase activity in affective psychosis and schizophrenia. Arch Gen Psychiatry1976; 33:585-591.
48.
48. Lykouras E, Markioanos M, Malliaras D, Stefanis C. Neurochemical variables in delusional depression. Am J Psychiatry1998; 145:214-217.
49.
49. O’Brien JT, Ames D, Schweitzer I, et al. Clinical, magnetic resonance imgaging and endocrinological differences between delusional and non-delusional depression in the elderly. Int J Geriatr Psychiatry1997; 12:211-218.
50.
50. Simpson S, Baldwin RC, Jackson A, Burns A. The differentiation of DSM-II-R psychotic depression in later life from nonpsychotic depression: comparisons of brain changes measured by multispectral analysis of magnetic resonance brain images, neuropsychological findings and clinical features. Biol Psychiatry1999; 45:193-204.
