title: The monoaminergic footprint of depression and psychosis in dementia with Lewy bodies compared to Alzheimer's disease.
abstract: BACKGROUND
  Depression and psychosis are two of the most severe neuropsychiatric symptoms (NPS) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Both NPS have negative effects on cognitive performance and life expectancy. The current study aimed to investigate and compare monoaminergic etiologies between both neurodegenerative conditions, given the lack of an efficient pharmacological treatment until present.
  
  
  METHODS
  Eleven behaviorally relevant brain regions of the left frozen hemisphere of 10 neuropathologically confirmed AD patients with/without depression (AD + D/-D; 5 were psychotic within AD + D), 10 confirmed DLB patients, all of whom were depressed (DLB + D; 5 psychotic patients), and, finally, 10 confirmed control subjects were regionally dissected. All patients were retrospectively assessed before death using the Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) and Cornell Scale for Depression in Dementia amongst others. The concentrations of dopamine (DA), serotonin (5-HT), (nor)adrenaline and respective metabolites, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), 5-hydroxy-3-indoleacetic acid (5-HIAA), and, 3-methoxy-4-hydroxyphenylglycol (MHPG), were determined using reversed-phase high-performance liquid chromatography with electrochemical detection.
  
  
  RESULTS
  DLB subjects had the overall lowest monoamine and metabolite concentrations regarding 33 out of 41 significant monoaminergic group alterations. Moreover, MHPG levels were significantly decreased in almost 8 out of 11 brain regions of DLB- compared to AD patients. We also observed the lowest 5-HT and 5-HIAA levels, and 5-HIAA/5-HT turnover ratios in DLB + D compared to AD + D subjects. Additionally, a 4- and 7-fold increase of DOPAC/DA and HVA/DA turnover ratios, and, a 10-fold decrease of thalamic DA levels in DLB + D compared to AD + D patients and control subjects was noticed. Regarding psychosis, hippocampal DA levels in the overall DLB group significantly correlated with Behave-AD AB scores. In the total AD group, DA levels and HVA/DA ratios in the amygdala significantly correlated with Behave-AD AB scores instead.
  
  
  CONCLUSIONS
  Monoaminergic neurotransmitter alterations contribute differently to the pathophysiology of depression and psychosis in DLB as opposed to AD, with a severely decreased serotonergic neurotransmission as the main monoaminergic etiology of depression in DLB. Similarly, psychosis in DLB might, in part, be etiologically explained by dopaminergic alterations in the hippocampus, whereas in AD, the amygdala might be involved.
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Wilrijk, Antwerp, 2610 Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Vermeiren
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Wilrijk, Antwerp, 2610 Belgium.
authors.forename: Debby
authors.initials: D
authors.lastname: Van Dam
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Wilrijk, Antwerp, 2610 Belgium.
authors.forename: Tony
authors.initials: T
authors.lastname: Aerts
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Wilrijk, Antwerp, 2610 Belgium ; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Lindendreef 1, Antwerp, 2020 Belgium.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
authors.affiliation: Biobank, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, Antwerp, 2610 Belgium.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.affiliation: Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Wilrijk, Antwerp, 2610 Belgium ; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Lindendreef 1, Antwerp, 2020 Belgium ; Department of Neurology and Alzheimer Research Center, University of Groningen, University Medical Center Groningen (UMCG), Hanzeplein 1, Groningen, 9713, GZ The Netherlands ; Biobank, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, Antwerp, 2610 Belgium.
authors.forename: Peter P
authors.initials: PP
authors.lastname: De Deyn