Neuropathological studies of serotonergic and noradrenergic systems in Lewy body disease patients with delusion or depression

The association between psychiatric symptoms in Lewy body disease (LBD) and the noradrenergic and serotonergic systems is still controversial. This study investigated the quantitative relationships of depression and delusion with these systems.

The accumulation of LBs in the DRN of individuals with LBD was associated with delusion, whereas a decrease in the number of neurons in the LC was associated with depressive mood. These neurodegenerative changes involved the serotonergic and noradrenergic systems and may be associated with the formation of delusion and depression, respectively, in LBD.

We studied 24 postmortem tissues from individuals with a pathological diagnosis of LBD with sufficient clinical history. The numbers of neurons and Lewy bodies (LBs) in the locus coeruleus (LC) and dorsal raphe nucleus (DRN) were counted, and the density of neurons in the DRN was analyzed. In addition, the densities of tryptophan hydroxylase-positive neurites and norepinephrine transporter-positive neurites in the amygdala and dorsal prefrontal cortex were measured. Finally, we divided the cases into two groups: with or without depressive mood, and with or without delusion. Quantitative histological data were compared between the groups.

The group with depressive mood had a significantly smaller number of neurons in the LC compared with the group without depressive mood. The group with delusion had a significantly larger number of LBs in the DRN compared with the group without delusion. The density of norepinephrine transporter-positive neurites in the dorsal prefrontal cortex was significantly correlated with the number of neurons in the LC. Conclusions: The accumulation of LBs in the DRN of individuals with LBD was associated with delusion, whereas a decrease in the number of neurons in the LC was associated with depressive mood. These neurodegenerative changes involved the serotonergic and noradrenergic systems and may be associated with the formation of delusion and depression, respectively, in LBD.