|Terms||Definition and Comments|
|Depression Heterogeneity||Depression is a highly heterogeneous syndrome driven by varying genetic and neurophysiological mechanisms, which give rise to varying symptom profiles, clinical trajectories, and treatment outcomes. This heterogeneity may be more apparent in late-life depression, because aging-related changes across multiple organ systems may contribute to depression (|
|Vascular Depression||A subtype of depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. A recent consensus report (|
14) suggested the following criteria for vascular depression: 1) evidence of vascular pathology in elderly subjects with or without cognitive impairment, 2) absence of previous depressive episodes preceding obvious cerebrovascular disease, 3) presence of cerebrovascular risk factors, 4) coincidence of depression with cerebrovascular risk factors, 5) clinical symptoms characteristic of vascular depression (executive dysfunction, decrease in processing speed, and lethargy), and 6) neuroimaging data confirming cerebrovascular disease. However, these diagnostic criteria for vascular depression are, until now, not widely accepted, and vascular depression has not been included in formal psychiatric manuals.
|Cerebral Microvascular Function and Dysfunction||Core functions of the cerebral microcirculation, defined as cerebral vessels with a diameter <150 μm (arterioles, capillaries, and venules), are to 1) optimize the delivery of nutrients and removal of waste products in response to variations in neuronal activity, 2) maintain the cerebral interstitial milieu for proper cell function, and 3) decrease and stabilize pulsatile hydrostatic pressure at the level of capillaries (|
17). Cerebral microvascular dysfunction is defined as an impairment in any of these functions.
|Blood-Brain Barrier||A tightly linked monolayer of endothelial cells, together with a basement membrane, astrocyte end feet, and mural cells (pericytes in capillaries and vascular smooth muscle cells in arterioles). The blood-brain barrier separates the circulating blood and brain compartments and strictly regulates blood-to-brain and brain-to-blood transport of solutes to maintain the highly controlled internal milieu of the central nervous system (|
|Neurovascular Coupling||Mechanism by which the brain can rapidly increase local blood flow to activated neurons (|
132). Upon an increase in neuronal activity, astrocytes signal to endothelial cells the paracrine release of vasoactive agents. These signals engage smooth muscle cells and, possibly, pericytes to induce vasodilatation, reduce cerebrovascular resistance, and increase local cerebral blood flow (
|Cerebral Autoregulation||Ability of the cerebrovasculature to maintain a constant level of global brain perfusion despite varying arterial blood pressure (|
22). This ensures a relatively constant level of blood flow to meet the high metabolic demand of the brain (
137). Arterioles together with larger cerebral arteries regulate this response by varying cerebrovascular resistance mediated by myogenic responses (
|Albumin Quotient||Ratio of cerebrospinal fluid albumin to serum albumin level. Albumin originate solely from the systemic circulation and cannot cross an intact blood-brain barrier. An increase in the albumin quotient can, thus, be used as an indirect measure of blood-brain permeability.|
|Cerebrovascular Reactivity||Change in flow in response to increased neuronal activity (i.e., neurovascular coupling) or a metabolic or vasodilatory stimulus, e.g., increase in partial pressure of carbon dioxide (|
138). This response reflects the ability of the cerebrovasculature, notably, arterioles and capillaries, to dilate in response to increased neuronal metabolic demand and is endothelium-dependent (
Functions of the Cerebral Microvasculature
Contribution of Microvascular Dysfunction to Depression
Evidence of Cerebral Microvascular Dysfunction in Depression
|Manifestation of Altered Cerebral Microvascular Function and Structure||Technique(s)||Findings in Individuals With Depression as Compared to Those Without|
|Increased Blood-Brain Barrier Permeability||Qalb; neuropathology||Increased blood-brain barrier permeability in cross-sectional studies (|
27). No prospective data available.
|Reduced Cerebral Vasoreactivity||TCD; ASL; SPECT||One prospective study (|
35) found that cerebral vasoreactivity increased the risk of depression. Most cross-sectional studies (
41), but not all (
42), also found reduced cerebral vasoreactivity. Most of these studies determined vasoreactivity at the level of a large cerebral artery.
|Impaired Cerebral Autoregulation||TCD||One cross-sectional study (|
44) found impaired cerebral autoregulation. No prospective data available.
|Altered Resting Cerebral Blood Flow||TCD; SPECT; ASL; PC-MRA||In two prospective studies (|
46), lower cerebral blood flow velocity, an indirect measure of blood flow, was associated with incident depression. No prospective data available on direct measures of cerebral blood flow. Cross-sectional studies (
49) found altered regional or global cerebral perfusion independently of cerebral atrophy.
|Retinal Microvascular Changes||DVA; fundoscopy||One prospective study (|
52) showed that lower flicker light–induced vasodilatation is associated with increased risk of depression, but another prospective study (
53) did not find associations between microvascular diameters and depression.
|Cerebral Small Vessel Disease||MRI: T1W, T2W, T2∗W, FLAIR; neuropathology||Meta-analyses (|
57) found that cerebral small vessel disease features increase the risk of depression. Results are stronger for features in frontal and subcortical regions. Neuropathology studies (
65) have found inconsistent results.
Blood-Brain Barrier Permeability
Cerebrovascular Reactivity, Cerebral Autoregulation, and Resting Cerebral Blood Flow
Retinal Microvascular Changes
Features of Cerebral Small Vessel Disease
Contribution of Microvascular Dysfunction to Apathy, Cognitive Dysfunction, and Stroke in Depression
Drivers of Microvascular Dysfunction in Depression: Aging, Psychological Stress, Arterial Stiffness and Hypertension, and Type 2 Diabetes and the Metabolic Syndrome
Psychological Stress and Inflammation
Arterial Stiffness, Hypertension, and Blood Pressure Fluctuations
Type 2 Diabetes and Metabolic Syndrome
Potential Therapeutic Targets and Interventions
- Kessing L.V.
- Rytgaard H.C.
- Ekstrøm C.T.
- Torp-Pedersen C.
- Berk M.
- Gerds T.A.