International Psychogeriatrics

Behavioral and Psychological Symptoms of Dementia (BPSD): A Clinical and Research Update
Pharmacologic Approaches

Neurobiology of Major Depression in Alzheimer's Disease

George S. Zubenko a1a2
a1 Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
a2 Department of Biological Sciences, Mellon College of Science, Carnegie-Mellon University, Pittsburgh, Pennsylvania, USA.

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zubenko g   [PubMed][Google Scholar] 

The original catecholamine hypothesis of affective disorders focused largely on the role of the noradrenergic components of the central nervous system in the etiology of depression and mania (Bunney & Davis, 1965; Schildkraut, 1965). Additional evidence from clinical, pharmacologic, and physiologic studies has emerged since the original hypothesis was proposed and generally supports the view that clinically significant depression can result from a dysfunction of central nervous system mechanisms employing the catecholamine neurotransmitters norepinephrine and dopamine (Jimerson, 1987; Siever, 1987). Neurochemical studies of serotonin (5-HT) receptors and 5-hydroxyindoleacetic acid (5-HIAA) in spinal fluid or brain tissue also suggest an alteration in serotonergic components of the central nervous system in both idiopathic major depression and suicide (Brikmayer & Riederer, 1975; Crow et al., 1984; Lloyd et al., 1974; Mendlewicz et al., 1981; Stanley & Mann, 1983). In contrast to these hypotheses, which suggest that depression may result from the decreased function of one or more central aminergic systems, the cholinergic hypothesis of affective disorders (Janowsky & Risch, 1987) posits that idiopathic depression is associated with the hyperfunctioning of cholinergic systems. This hypothesis is especially interesting in the context of Alzheimer's disease (AD) because the progression of the central cholinergic deficit that occurs in this disorder may interact with the pathophysiology of depression to limit the prevalence of major depression in later stages of this disorder.