Patients with Depression Show Increased Volume in Left Hypothalamus

Investigators at the Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS) in Leipzig, Germany, found that the volume of the left hypothalamus was about 5% greater in patients with major depressive or bipolar disorders compared to their healthy counterparts.

In a surprising development, when the team conducted magnetic resonance imaging (MRI) on living patients, the results failed to support findings from previous postmortem investigations of the region. Those studies showed that hypothalamus volumes were smaller or level in patients with bipolar disorder or major depressive disorder (MDD).

“Contrary to our expectations, the hypothalamus volume was increased in patients with uni- and bi-polar affective disorders,” the authors wrote.

The hypothalamus region of the brain maintains the balance of autonomic, endocrine, and behavior functions. The area controls body temperature, thirst, and hunger and is involved in sleep and emotions.

“As head of the hypothalamus-pituitary-adrenal axis (HPA) the hypothalamus links the emotional, limbic, and cortical centers of the brain,” Planck investigators and colleagues from the Department of Psychiatry and Psychotherapy of the University Clinic in Leipzig said in the journal Acta Psychiatrica Scandinavica.

Normally, a stressful event triggers an increase in cortisol to provide the body with more energy to combat the challenge. Control mechanisms in the HPA axis then ensure that the system returns to a balanced state when the threat passes.

In some individuals with depressive disorders, however, the stress response operates ``at full throttle’’ even when no stressful situation is apparent because of malfunctions in the feedback mechanism.

“In these patients with MDD, the HPA axis is overactive due to inherited or acquired traits,” the authors said. “Too much cortisol is released during stress, which causes adverse structural changes in brain regions that control the HPA axis, ultimately leading to a disinhibition of the HPA axis.”

The underlying reason for this hyperactive stress response system and the role of the hypothalamus as its control unit has remained unclear, the authors said.

To investigate, the team conducted a cross-sectional study involving 61 patients with depressive disorders and 23 controls. Twenty of the patients with depression were medicated, 20 were unmedicated and 21 had bipolar disorder. Twenty of the controls were matched to the unmedicated MDD patients.

The investigators then acquired seven Tesla-T1 weighted magnetic resonance images and processed them using methods that they said yielded highly precise volume levels of the hypothalamus. This showed the 5% volume increase in the left side among the patients with depression compared to the controls.

“The volume difference existed independent of medication status and statistical correction for intracranial volume,” the authors wrote.

Further, the team found that among the medicated patients with depression, the left hypothalamus volume correlated with the severity of the disease.

Why might this be the case, when prior studies indicated a volume decrease?

“Previous data, which led to our hypothesis of reduced hypothalamus volumes in mood disorders, have been very limited, presumably because the hypothalamus is notoriously difficult to distinguish from its surroundings with common neuroimaging techniques,” the team wrote.

The researchers noted that a recent animal study showed that large hypothalamus volumes are associated with stress susceptibility in chronically stressed mice.

In light of existing data that suggest the stress response may be associated with structural and functional asymmetry of the brain, “It seems possible that specifically a unilateral enlargement of the hypothalamus is related to HPA axis activity and depressive symptomology,” the authors wrote.

“More research is clearly needed to formulate advanced hypotheses,” they added.