According to the World Health Organization, 322 million people worldwide were affected by depression in 2015. In the U.S., 16.1 million adults aged 18 years or older had experienced at least one major depressive episode in the last year, which represented 6.7 percent of all adults.

Depression, a leading psychiatric disorder, is also the leading cause of disability among people ages 15-44 years. Major Depressive Disorder is the most commonly diagnosed form of depression. Although the cause remains unknown, it is thought that depression results from a chemical imbalance, but the disease itself may be more complex.

Research suggests that depression doesn't develop from simply having too much or too little of certain brain chemicals. Many causes are possible, including faulty mood regulation by the brain, genetic vulnerability, stressful life events, medications, and medical problems. In fact, it may be that several of these forces interact to bring on depression.

More important than levels of specific brain chemicals, researchers believe that nerve cell connections, nerve cell growth, and the functioning of nerve circuits have a major impact on depression. Still, their understanding of the neurological underpinnings of mood is incomplete.

Researchers do know that people more predisposed to depression show a dysregulation of the endogenous stress response system — the hypothalamic-pituitary-adrenal axis (HPA), which is normally triggered during a stressful situation. During stress, the amount of cortisol is increased until the situation has passed when several control mechanisms in the HPA axis ensures that the system returns to a balanced state.

But in those with depression who are more disposed to stress, this is not the case. In these people, a malfunction of the feedback mechanism results in a stress response operating at full speed, even when there is no stressful situation. Until now, however, the underlying reason for this hyperactive stress response system and the role of the hypothalamus as the control unit has remained somewhat of a mystery.

In a recent study, scientists at the Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS) in Leipzig, Germany, and the Department of Psychiatry and Psychotherapy of the University Clinic in Leipzig found that in people with an affective disorder, the left hypothalamus is about 5 percent larger than that of those in healthy people. The cross‐sectional study included 20 unmedicated patients, 20 medicated patients with major depressive disorder, 21 patients with bipolar disorder, and 23 controls.

Seven Tesla, T1‐weighted magnetic resonance images were acquired and processed using methods specifically developed for high‐precision volumetry of the hypothalamus. The severity of disorders was measured using standard questionnaires and interviews.

The researchers observed that this brain region was enlarged in people with depression as well as those with bipolar disorder. In one of the groups of patients with depression, the more severe the depression, the larger the hypothalamus.

Medication did not have any effect on the size of the hypothalamus. Although studies have shown that this brain structure is more active in people with depression and bipolar disorder, it is not clear what role a large hypothalamus plays.

It could be that higher activity leads to structural changes that may explain why many who suffer with depression or bipolar disorder show increased levels of cortisol and are prone to periods of intense tension.