The locus coeruleus in schizophrenia: a postmortem study of noradrenergic neurones

Abstract

Despite evidence for an abnormality of noradrenergic function in schizophrenia, it remains unclear whether the number of noradrenergic neurones is normal in patients with the disorder. In postmortem, formalin-fixed tissue from 15 schizophrenic patients and 18 controls matched for age and gender, we made estimates of the number and size of tyrosine-hydroxylase-immunoreactive cells in the locus coeruleus (LC). No significant difference was detected between these groups in the cross-sectional area or diameter of immunoreactive cell profiles. Profile number was not significantly affected by gender, side of the brainstem (left or right), postmortem interval or time in formalin; however, the levels of immunoreaction product (optical density) correlated significantly with our profile counts, which were lower on average in the schizophrenic group. When optical density was included as a covariate in our comparison (a repeated-measures analysis of variance) of schizophrenic and control cases, we found no difference between these groups in the number of neurones counted. An age-related decrease in profile number was detected, but no effect of age on our estimates of cell size was apparent. Our results highlight the importance of accounting for potential confounding variables, including variations in the quality of immunostaining, in investigations of this type. The findings presented here concur with previous studies suggesting that noradrenergic dysfunction in schizophrenia is not associated with an anatomical abnormality at the level of the LC.

Central Nervous System Circuitries Underlying Two Types of Peripheral Autonomic Nervous System Disorders~!2008-04-24~!2008-09-26~!2008-12-05~!

“…This phenomenon is consistent with others showing that the number of neurons of the A5(NA) and C1(Ad) nuclei is completed by birth [93,[100][101][102][103] whereas the number of A6(NA) neurons do not reach totality until adultness [104][105][106][107][108][109][110][111][112][113][114]. Furthermore, these neurons fade gradually with aging [104,107,115]. This fading is paralleled by the underactivity of the C1(Ad) nuclei in such a way that aging is always accompanied by the progressive predominance of the A5(NA)-neural sympathetic activity.…”

Age-related Changes in Locus Ceruleus on Neuromelanin Magnetic Resonance Imaging at 3 Tesla

“…[12][13][14][15] In Parkinson's and Alzheimer's diseases, neurons are lost and intraneuronal neuromelanin is diminished. [9][10][11] On the other hand, in depression and schizophrenia, subtle changes were observed in neuronal number or size and in enzyme activities that suggested dysfunction of the noradrenergic system.…”

“…[9][10][11] On the other hand, in depression and schizophrenia, subtle changes were observed in neuronal number or size and in enzyme activities that suggested dysfunction of the noradrenergic system. [12][13][14][15] We believe that neuromelanin MR imaging has the potential to detect organic or functional changes in the LC in the above-cited disorders as a reduction in the neuromelaninproduced contrast from decreased cell number and W or intracellular neuromelanin concentration. 5 However, signal changes that occur during pathological conditions should be carefully evaluated by considering age-dependent signal ‰uctuations.…”

Why patients with Alzheimer’s disease may show increased sensitivity to tropicamide eye drops: role of locus coeruleus

“…It has been suggested that the anatomical substrate of the age-and disease-dependent alterations in pupil function may be the noradrenergic locus coeruleus (LC) (Prettyman et al 1997). Indeed, it is well documented that pupil diameter shows a monotonic decline with age (Bourne et al 1979;Loewenfeld 1979;Smith 1992;pp 407-479, 488-517, 1131pp 407-479, 488-517, -1187pp 407-479, 488-517, and 1200pp 407-479, 488-517, -1203pp 407-479, 488-517, in Loewenfeld 1993, and this is paralleled by a decline in cell numbers in the LC (Vijayashankar and Brody 1979;Tomlinson et al 1981; Lohr and Jeste 1988;Chan-Palay and Asan 1989;Manaye et al 1995;Craven et al 2005). Moreover, neurones in the LC are especially vulnerable to the degenerative process in AD.…”