New research reveals that increased inflammation, indicated by higher levels of a protein called VCAM-1, is associated with decreased gray matter and altered brain connectivity in patients with major depressive disorder (MDD).
These brain changes also correlate with VCAM-1 levels.
Key Facts:
- MDD patients had higher blood VCAM-1 levels than healthy controls
- Higher VCAM-1 related to decreased gray matter in emotion regulation areas
- VCAM-1 mediated lowered gray matter and heightened brain connectivity in MDD
- Suggests inflammation impacts brain regions involved in depression
Source: J Affect Disord. (2023)
Brain Regions Showing Gray Matter Loss Are Linked to VCAM-1
A new study uncovered an association between increased systemic inflammation and decreased gray matter volume (GMV) in brain regions related to emotion regulation in patients with major depressive disorder (MDD).
The research team analyzed blood levels of vascular cell adhesion molecule-1 (VCAM-1), a protein that rises during inflammation and indicates dysfunction of the cells lining blood vessels.
They compared VCAM-1 levels between 85 patients diagnosed with MDD and 80 healthy individuals.
Using brain imaging, the researchers also mapped gray matter volume and functional connections across brain regions in the two groups.
Gray matter areas contain neuron cell bodies that process information.
The investigators found that the MDD patients exhibited significantly higher blood VCAM-1 levels compared to healthy controls.
In terms of brain structure, patients showed lowered GMV in regions including the medial prefrontal cortex, which is involved in decision making and emotional processing, and the postcentral gyrus located in the parietal lobe.
GMV in these areas negatively correlated with VCAM-1 levels, meaning higher inflammation related to lower gray matter.
Altered Brain Connectivity Also Linked to Inflammation
Along with investigating volumetric changes, the researchers analyzed functional connectivity between brain areas, which gives insight into communication between regions.
The analysis revealed increased connectivity between two regions – the ventral prefrontal cortex, important for emotional regulation, and the inferior parietal lobe, which contributes to attention processing – in MDD patients compared to healthy controls.
Notably, the heightened communication between these two areas trended positively with VCAM-1 levels, though more research is needed to confirm this relationship.
VCAM-1 May Contribute to Gray Matter and Connectivity Changes
To assess whether VCAM-1 plays a role in the observed brain alterations, the team conducted mediation analyses.
This statistical technique evaluates whether a third variable drives the relationship between two other variables.
The mediation testing suggested that VCAM-1 mediated the lowered postcentral gyrus gray matter and heightened ventral prefrontal cortex-inferior parietal lobe connectivity related to MDD.
In other words, inflammation as measured by VCAM-1 may contribute to these brain changes associated with the disorder.
Implications: Inflammation Impacting Emotion Centers
This research highlights links between inflammatory factors in the blood and structural and functional brain changes related to major depression.
The affected areas include emotion and attention hubs that show differences in MDD.
Though further confirmation is required, the results suggest circulating inflammatory signals may reach the brain and influence regions involved in the regulation of mood and emotions.
Measuring inflammatory biomarkers along with analyzing associated brain changes could aid diagnosis and monitoring of MDD.
Understanding these mechanisms may also inform new treatment targets in the future.
Overall this pioneering study significantly advances knowledge of how inflammation interacts with neural substrates of depression.
Moving forward, longer-term studies tracking inflammatory markers, brain changes, and symptoms over time can help clarify causal relationships.
How Might Inflammation Impact the Brain in Depression?
This research provides intriguing clues into how peripheral inflammation could induce changes in brain structure and function related to major depressive disorder (MDD).
But how might circulating inflammatory factors like VCAM-1 exert effects on emotional and cognitive control centers deep in the brain?
Previous studies suggest that inflammatory signaling can occur through several pathways.
Direct Transport Across the Blood-Brain Barrier
Inflammation prompts vascular cells to produce adhesion factors enabling immune cells to penetrate the blood vessel lining known as the blood-brain barrier (BBB) and enter brain tissue.
Proinflammatory molecules like cytokines may also directly cross the BBB.
Activation of Brain Immune Cells
Circulating inflammatory proteins can activate the brain’s resident immune cells, microglia and astrocytes.
Activated glial cells drive neuroinflammation and may damage synapses and neurons.
Signaling Through the Vagus Nerve
The vagus nerve connects the body to the brainstem. Inflammatory factors may stimulate vagal nerve fibers, transmitting signals to brain regions involved in mood regulation.
Through these mechanisms, elevated VCAM-1 and other inflammatory mediators likely stimulate neuroinflammation and neurovascular dysfunction, eliciting downstream structural and functional changes.
Mood Disorders & Inflammation: A Bi-Directional Relationship
While this research found that increased peripheral VCAM-1 related to decreased gray matter and altered connectivity in MDD patients, inflammation may also arise from mood disorders themselves.
Stress activates inflammatory responses through the sympathetic nervous system and hormonal pathways.
Depression involves excessive activation of stress systems, which research shows can prompt sustained low-grade inflammation.
In turn, neuroinflammation and an “inflammatory phenotype” are thought to play a driving role in the onset of multiple psychiatric illnesses.
So in reality, the association between mental health conditions and inflammation likely involves complex bi-directional interactions.
Unraveling these relationships remains an active area of research that will inform treatment innovations.
References
- Study: Elevated VCAM-1 levels in peripheral blood are associated with brain structural and functional alterations in major depressive disorder
- Authors: Zhou et al. (2023)
