Brain volume abnormalities and neurocognitive deficits in diabetes mellitus: Points of pathophysiological commonality with mood disorders?

Mood Disorders/Psychopharmacology Unit, University Health Network, University of Toronto, 399 Bathurst Street, Toronto, Ontario, Canada.
Advances in Therapy (Impact Factor: 2.27). 04/2010; 27(2):63-80. DOI: 10.1007/s12325-010-0011-z
Source: PubMed


It is hypothesized that diabetes mellitus (DM) and mood disorders share points of pathophysiological commonality in the central nervous system.
A PubMed search of all English-language articles published between 1966 and March 2009 was performed with the following search terms: depression, mood disorders, hippocampus, amygdala, central nervous system, brain, neuroimaging, volumetric, morphometric, and neurocognitive deficits, cross-referenced with DM. Articles selected for review were based on adequacy of sample size, the use of standardized experimental procedures, validated assessment measures, and overall manuscript quality. The primary author was principally responsible for adjudicating the merit of articles that were included.
Volumetric studies indicate that individuals with Type 1/2 DM exhibit regional abnormalities in both cortical and subcortical (e.g., hippocampus, amygdala) brain structures. The pattern of neurocognitive deficits documented in individuals with Type 1 DM overlap with Type 2 populations, with suggestions of discrete abnormalities unique to each phenotype. The pattern of volumetric and neurocognitive deficits in diabetic populations are highly similar to that reported in populations of individuals with major depressive disorder.
The prevailing models of disease pathophysiology in DM and major depressive disorder are distinct. Notwithstanding, the common abnormalities observed in disparate effector systems (e.g., insulin resistance, immunoinflammatory activation) as well as brain volume and neurocognitive performance provide the nexus for hypothesizing that both conditions are subserved by overlapping pathophysiology. This conception provides a novel framework for disease modeling and treatment development in mood disorder.

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    • "Our mediation findings extend prior findings linking peripheral physiological changes associated with the MetS and depressive symptomatology by identifying a potential mediating factor: reduced globus pallidus volume. As noted previously, this observation is consistent with prior findings and speculations that the MetS and depressive symptoms may share common pathophysiological features [22], including alterations in central neurotransmitter systems that covary with metabolic dysregulation [58] [59] and risk for depressive symptoms [81], as well as volume reductions in basal ganglia regions [74] [82]. Again, however, the causal directions of associations and temporal ordering of depressive symptoms, volumetric changes, and depressive symptoms need to be tested in future longitudinal research. "
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    • "Diabetes may place patients at risk for depression through a biological mechanism linking the metabolic changes of DM to changes in the CNS.9 Keeping with this perspective, McIntyre et al10 demonstrated that a common point of pathophysiology exists between MDD and DM when considering brain volume abnormalities and neurocognitive deficits. In this review, we discuss the literature pertinent to EEG abnormalities in DM, but we also discuss biological mechanisms underlying each EEG parameter discussed, in order to evaluate whether or not a common link exists between neurobiological mechanisms associated with EEG findings in DM and in MDD. "
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    • "Severe hypoglycemia leads to uncontrolled release of excitatory amino acids, such as glutamate and aspartate, triggering a cascade of events that may result in neuronal damage (1), whereas chronically elevated glucose levels induce a form of glucose neurotoxicity (2). Variations in insulin and counterregulatory hormone levels may also be neurotoxic (3,4). "
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