What hormone is responsible for sadness?

There are a few key hormones that play an important role in regulating human emotions like sadness. The main ones are serotonin, dopamine, oxytocin, and cortisol. Let’s take a closer look at each of these hormones and how they impact sadness.


Serotonin is one of the most well-known hormones involved in mood regulation. It is a neurotransmitter that is produced in the brain and plays a key role in regulating emotions. Low levels of serotonin have been linked to increased feelings of sadness and depression. Here are some quick facts about serotonin:

  • Serotonin is synthesized from the amino acid tryptophan.
  • It is primarily produced in the raphe nuclei of the brainstem.
  • Serotonin binds to receptors throughout the brain, particularly in the limbic system which regulates emotion.
  • Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants that work by blocking the reabsorption of serotonin, increasing its levels in the brain.

When serotonin levels drop, it can disrupt emotional regulation and lead to feelings of sadness, emptiness, and depression. Research shows that people with depression often have lower levels of serotonin activity in the brain. So in summary, low serotonin is strongly linked to increasing sadness.


Dopamine is another neurotransmitter that is involved in mood regulation. Dopamine plays a key role in regulating the brain’s reward and pleasure centers. Like serotonin, low levels of dopamine have been associated with sadness and a lack of motivation or interest in life:

  • Dopamine is synthesized from the amino acid tyrosine.
  • It is produced in several areas like the substantia nigra and ventral tegmental area.
  • Dopamine binds to receptors that regulate motivation, pleasure, and cognition.
  • Parkinson’s disease is characterized by low dopamine levels.
  • Depressed individuals often show decreased dopamine activity.

When dopamine levels are too low, people can experience anhedonia, which is a lack of interest or pleasure in normally enjoyable activities. This can contribute to feelings of sadness, emptiness, and depression as well.


Oxytocin is a neuropeptide hormone that is involved in social bonding, reproduction, and childbirth. Unlike serotonin and dopamine, high levels of oxytocin can lead to increased feelings of sadness:

  • Oxytocin is synthesized in the hypothalamus and secreted into the bloodstream.
  • It binds to oxytocin receptors in the brain, uterus, and breasts.
  • Oxytocin facilitates social bonding, maternal behaviors, and pair bonding.
  • Higher oxytocin levels have been observed in depressed individuals.
  • Elevated oxytocin may intensify feelings of sadness and grief.

Oxytocin increases bonding and attachement. Therefore, when we experience loss through death, divorce, or distance from loved ones, high oxytocin levels may amplify feelings of sadness and grief. Crying also releases oxytocin, which can prolong sadness.


Cortisol is a steroid hormone released by the adrenal glands as part of the body’s stress response system. Prolonged high cortisol levels are linked to increased sadness and disturbed mood:

  • Cortisol is synthesized from cholesterol in the adrenal glands.
  • It is released into the bloodstream to mobilize energy reserves and regulate metabolism.
  • Cortisol is regulated by the hypothalamic-pituitary-adrenal (HPA) axis.
  • Chronically high cortisol can be caused by excessive stress.
  • Elevated cortisol impairs cognition, immune function, and mental health over time.

When cortisol levels remain too high for too long, it can lead to impaired cognitive function, anxiety, irritability, and increased feelings of sadness. Basically, chronic stress and elevated cortisol takes a toll on mental health.

Other Hormones

While serotonin, dopamine, oxytocin and cortisol play major roles, there are a few other hormones that may contribute to sadness to a smaller degree:

  • Norepinephrine – This neurotransmitter influences mood, stress response and attention. Low norepinephrine may decrease motivation.
  • Estrogen – Estrogen fluctuations in women can influence mood and sadness, especially around menstruation and menopause.
  • Testosterone – Low testosterone in men has been associated with depressive symptoms.
  • Melatonin – The sleep hormone melatonin regulates circadian rhythms. Disrupted sleep can impact mood.

These hormones have smaller effects on mood compared to serotonin, dopamine, oxytocin and cortisol, but imbalances may still contribute to sadness overall.

The HPA Axis

The hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role in regulating hormone levels and the stress response. Dysfunction of the HPA axis has been implicated in depression:

  • Triggered by stress, the hypothalamus releases CRH hormone.
  • CRH stimulates the pituitary to secrete ACTH hormone.
  • ACTH acts on the adrenal glands to produce cortisol.
  • Cortisol provides negative feedback to the hypothalamus and pituitary.
  • In depression, this feedback loop may be disrupted, leading to chronically high cortisol.

Imbalances in the HPA axis communication between the hypothalamus, pituitary and adrenal glands can lead to hormone dysregulation that may increase sadness and the risk of mood disorders.

Genetic Factors

Research suggests genetics play a significant role in depression and sadness. Family history and gene polymorphisms can influence hormone levels and receptor function:

  • A serotonin transporter gene called 5-HTTLPR has short and long variants; the short version is linked to increased depression risk.
  • The val66met BDNF gene variant affects dopamine activity and is associated with depression susceptibility.
  • Genetic variations in estrogen receptors may lead to mood disturbances in women.
  • Childhood trauma can epigenetically alter genes that regulate stress hormones.

While genetics are not the sole cause of sadness, DNA and epigenetics can make some individuals more vulnerable to hormone imbalances or environmental factors that disrupt mood.

Key Takeaways

In summary, here are some key takeaways on hormones and sadness:

  • Low serotonin levels are strongly associated with increased feelings of sadness and depression.
  • Low dopamine activity can cause anhedonia and contribute to sadness.
  • High oxytocin amplifies feelings of grief and sadness after loss or separation.
  • Prolonged elevated cortisol due to chronic stress raises depression risk.
  • Imbalances in the HPA axis can lead to hormone dysregulation.
  • Genetics play a role in depression susceptibility and hormone receptor function.
  • Overall, sadness is complex but often tied to low serotonin and dopamine, high oxytocin and cortisol, and genetic factors.

Treatments for Sadness

Since hormone imbalances play a key role in sadness and depression, some medical treatments target these directly:

Treatment Mechanism
SSRIs Increase serotonin
SNRIs Increase serotonin and norepinephrine
NDRIs Increase norepinephrine and dopamine
Oxytocin nasal spray Regulate oxytocin levels
Cortisol blockers Reduce excess cortisol

Psychotherapy and lifestyle changes like exercise, meditation, and stress management can also help restore hormone balance. Overall, addressing any hormone deficiencies or excesses contributing to sadness is key.


Feelings of sadness and depression result from complex interactions between multiple hormones, particularly serotonin, dopamine, oxytocin, and cortisol. Low levels of serotonin and dopamine, high levels of oxytocin and cortisol, genetic factors, and disruption of the HPA axis have all been implicated in sadness and depression. Treatments aim to restore hormone balance through medications, lifestyle changes, and psychotherapy. While sadness is a normal human emotion, profound or persistent sadness caused by hormone imbalances may require medical treatment.

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