Anxiety, depression and neurogenesis

It is interesting to tackle the pathologic phenomenon of anxiety and depression that more and more people are suffering from around the world, the occidental world particularly (just consider for example the increasingly higher use of psychotrop drugs in developped countries, however keeping in mind these uses aren't always justified in a therapeutic point of view).

My reading of the book "Neurosciences : exploring the brain" has brought me to think about the mecanisms of depression , in a neurological point of view, and about the standard ways used to cure it. Moreover, I've had the opportunity in an other indepandant part of this book to discover the neurogenesis mecanisms in mammals (neurons generation inside the brain), with a particular focus on the potential factors enhancing this neurogenesis. I propose in this article to make the mecanisms of anxiety and depression converge with the mecanisms of neurogenesis, and then to open a new way in curing this disease.

• Anxiety and depression

Anxiety is a negative, emotive manifestation that comes in a neurological way from the part of the brain named amygdala. The amygdala is located in the temporal lobs of the brain, just below the cerebral cortex.

The neurological pathway that involves in anxiety can be specified like this :
- the cerebral cortex (visual cortex, auditive cortex...) get some environmental stimuli
- these stimuli are integrated by the amygdala that synthesizes them; all the past elements of memory of the subject are also integrated by the amydala during this stimuli synthesis (traumatisms, education....)
- neuronal excitation of the hypothalamus by the amygdala
- secretion of CRH (corticotropine releasing hormone) hormone by the hypothalamus
- pituitary activation by the CRH involving in ACTH delivery (adrenocorticotropic hormone)
- ACTH action upon adrenal glands (just above the kidneys) that delives cortisol
Cortisol is the standard stress hormone that will act upon the whole sympathic and parasympathic system; then physical manifestations of anxiety will appear : increased blood pressure and cardiac frequency, sweat, digestive system slowed down... Cortisol will also act upon the hippocampus as a feedback. The hippocampus is a part of the brain located in the medial temporal lobe. The hippocampus activation inhibits the delivery of CRH hormone by the hypothalamus, that leads to a decrease of ACTH delivery by the pituitary and then to a slower activation of surenals and a decreased cortisol delivery.

Depression is a mental illness that affects 5% of the population in a year. The cardinal symptoms are lowered mood and decreased interest or pleasure in all activities. Other symptoms also occur : lost of appetite or increased appetite, insomnia or hypersomnia, fatigue, recurrent thoughts of death, diminished ability to concentrate. Episodes of major depression are often precipitated by stressful life events. If we measure the cortisol and ACTH hormones in blood samples from depressive patients, and in the same way CRH hormone, we find higher results than that obtained from normal healthy volunteers. In fact, if the amygdala stimulates too much the hypothalamus (constant and important stress), cortisol delivery is high and constant considering the CRH - ACTH - cortisol axis. Moreover, high blood concentration of cortisol has negative effects on the hippocampus, that become unable to regulate the hypothalamus : decreased cerebral hippocampus volume, a decreased neuronal neurotransmitters concentration (for exampe serotonin), and sometimes a neuronal degeneration. The depression vicious circle is then established, because the stress regulation system becomes inoperant through the broken feedback regulation of the hypothalamus by the hippocampus.

Standard treatments for depression acts upon the following pathways :
- a decreased excitation of the hypothalamus by the amygdala through anxiolytics and psychotherapies
- a hippocampus neuronal context dynamization by antidepressants (specially of the SSRI family, like Prozac)
Anxiolytics will decrease the amygdala excitation by inhibating the cortical activity (stimuli, "bad thoughts"); psychotherapies will work upon the decrease of the amygdala activity, giving the patient the opportunity to control in a cortical way its excitation (psychologic work about fear and stress management).

• Neurogenesis

Neurogenesis is the creation of neurons inside parts of the brain, coming from cerebral stem cells. The neurogenesis principles have been studied at first in mammals during standard brain development phases, foetal phase and early childhood. Recent experimentations have however demonstrated that brains from adult rats, that were living into a positive-stimulations loaded environment (games, toys, strong social life, colors...) show signs of hippocampus neurogenesis : new neurons were produced in this specific part of the brain. Moreover, an increased physical activity was enhancing this neuronal generation inside the hippocampus.

The experiments discovered finally that this particular mecanism was also valid for the human being : a rich, positively stimulating environment, associated with an increased physical activity involves in a hippocampus neurogenesis. Keep in mind that before, one thought that neurogenesis was only possible during antenatal and early childhood phases of life.

• Proposition

On the one hand, a caracteristic and common element finded in depressive patients is a hippocampus neuronal context attack : decreased neurotransmitters concentrations, neuronal degenerations, reduction in the hippocampus global volume. Antidepressants are used to redynamize the altered neurons in a depressed hippocampus. On the other hand, a rich, positively stimulating environment and an increased physical activity involves in a strong neurogenesis inside the hippocampus of healthy people. So we can conclude that in a neurological way putting a depressed patient into a positively stimulating environnement and making him doing physical activity will have benefic effects upon anxiety and resulting depression.

Anxiety/depression	Amygdala	Hippocampus
Enhancing factors	Too much excitation (global stress, trauma...)	Neuronal degeneration and neurotransmitters decrease partially due to an excess of cortisol
Inhibiting factors	Activity inhibition (anxiolytics, decreased negative stimuli, therapies involving a cortical regulation of the amygdala)	Neuronal reactivation and neurogenesis enhanced by antidepressants, sport and positive environmental stimuli

References : "Neurosciences : exploring the brain" by Mark F. Bear, Barry W. Connors, Michael A. Paradiso