The role of leptin in the development of depression

Today, there is much debate in the scientific community about the role of the pituitary-pituitary-adrenal system, which is directly related to leptin, inflammation, and depression. In this situation, immunologically active proteins become biomarkers of depression, and this gives them a special value.


  1. Leptin and adiponectin.
  2. Relationship of hormones to depression.
  3. Results.

Leptin and adiponectin

Fat tissue is the main source of leptin. It is a hormone with proinflammatory and anorexigenic qualities, participating in the correction of the hypothalamic-pituitary-adrenal system (HPA or Hypothalamic-pituitary-adrenal axis).

Leptin successfully crosses the blood-brain barrier through receptors that are widely activated in the brain, including – hypothalamus and amygdala. Adiponectin is also a lipid production. It has, for the most part, anti-inflammatory properties. The hormone is found in the cerebrospinal fluid (CSF), and its receptors are expressed in the human pituitary, hypothalamus, and human hippocampus.

Relationship of hormones to depression

Both hormones in the periphery change their values over the course of the day, but are mostly stable values. Nevertheless, the concentration of leptin in the blood is affected even by sleep patterns, not to mention eating behavior. Therefore, there is a definite relationship between the hormone level and antipsychotics. We know from scientific data that leptin concentration is significantly elevated in patients suffering from depression, so it makes sense to include a leptin diet and correct the eating behavior of patients in the treatment of these conditions even before taking antidepressants.

There is also evidence that some antidepressants increase leptin levels. But by and large, all of this data is contradictory. One study, for example, suggests that leptin concentrations are protective in childbirth, while another suggests that they are a factor in postpartum depression risks. One thing is certain: Peripheral leptin values are correlated with C-reactive protein.

Adiponectin concentrations have no association with depression, but most researchers report low blood levels of the hormone. There are also isolated indications of increased blood concentrations of the hormone 10 days after childbirth. This is most likely evidence that adiponectin levels correlate with the rate of progression of depression.

Note that the hormone also crosses the blood-brain barrier (BBB), but its plasma concentration may not reflect the levels of the hormone isoforms in the cerebrospinal fluid (CSF).  The isoforms are high, medium, and low molecular weight variations of the hormone.  The high molecular weight adiponectin most likely does not overcome the BBB, and the other two remain stable in the cerebrospinal fluid in obesity, even at low concentrations of adiponectin.


The association of leptin levels with body mass index suggests an association of the hormone with depression and abdominal obesity. In this case, signaling with low levels of the hormone is associated with a high risk of depression. The fact that resistance to leptin may be the target of therapy in obese and depressed patients indirectly receives evidence with Fluoxetine therapy for depression. It immediately increases the sensitivity to leptin of brain-derived neurotrophic factor activation.

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