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

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.