Depression, anxiety and post-traumatic stress disorder (PTSD) affect millions of people around the world. Although the exact mechanisms of these diseases are not fully understood, there is growing evidence that hormones may influence a person's susceptibility to these diseases. Researchers have identified specific neurons responsible for controlling how growth hormone affects the production of anxiety and fear memories, a hallmark of post-traumatic stress disorder. The discovery could lead to a new class of anti-anxiety drugs.
A new study by researchers at the University of São Paulo (USP) in Brazil provides a better understanding of the role of a hormone - growth hormone (GH) - in anxiety disorders, identifying for the first time the neurons responsible for mediating the effects of GH on neuropsychiatric disorders such as anxiety, depression and post-traumatic stress disorder.
"Our discovery of the anxiolytic (anxiety-reducing) mechanism of GH provides a possible, merely chemical, explanation for why patients who secrete more or less GH are more or less susceptible to these diseases," said José Donato Júnior, corresponding author of the study.
The somatic cells of the pituitary gland secrete adrenocorticotropic hormone, which is mainly controlled by growth hormone-releasing hormone (GHRH), somatostatin (SST), and gastrin. The former is secreted by the hypothalamus to stimulate the release of adrenocorticotropic hormone, and the latter is secreted by various tissues throughout the body to inhibit the release of adrenocorticotropic hormone.
Fear-related disorders, such as panic disorder, phobias, and post-traumatic stress disorder, are characterized by pathological fear responses resulting from exposure to intense fear-inducing events, resulting in the formation of "fear memories" in the hippocampus and amygdala. Gastrin plays a role in this.
Donato said: "The role of gastrin in post-traumatic stress has been studied for some time. Studies have shown that under chronic stress, gastrin-induced GH secretion is increased, which is beneficial to the formation of fear memory and post-traumatic stress in the animal brain."
The same goes for SST. Although studies have shown that SST-expressing neurons in the amygdala are associated with changes in anxiety and fear memory, it is currently unknown whether these neurons respond to and mediate the effects of GH in regulating anxiety and fear memory. That's exactly what the researchers wanted to investigate.
They found that in mice, about 60% of SST-expressing neurons in the amygdala responded directly to GH. In adult male and female mice in which the GH receptor gene was knocked out in SST-expressing neurons, male mice showed more anxiety-like behavior, while female mice showed no change in anxiety. In the absence of GH receptors, fear memory was significantly reduced in both male and female mice.
The study did not give a reason for the gender differences.
"We think this may be related to sexual dimorphism," Donato said. "We know that the areas of the brain that contain the neurons we studied are somewhat different in men and women. Some neurological diseases also differ in men and women, but perhaps not because of the changes."
The findings suggest that anxiety, post-traumatic stress and fear memories are different aspects of the same brain circuit.
"All this happens in the same neuronal population, which expresses GH receptors. In our experiments, when we turned off GH receptors, the mice had less fear memory. This means that the ability to form fear memories is impaired. It may be that GH is responsible for the development of post-traumatic stress," Donato said.
The researchers say the knowledge gained from the study could be used to develop a new class of anti-anxiety drugs. Furthermore, since GH secretion decreases with age, further studies should investigate potential links between GH, SST neurons, and neuropsychiatric disorders during aging. However, the next step for the researchers is to study the role of GH during pregnancy.
"We know that one of the peaks in GH secretion occurs during pregnancy," Donato said. "We also know that the incidence of depression increases during this period due to postpartum depression. Of course, these disorders also reflect social, economic and other stresses, but we must not forget that increased hormonal secretion during pregnancy and postpartum can cause brain dysfunction and can lead to these types of mental illnesses."
The research was published in the Journal of Neuroscience.