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Context: Researchers continue to research the causes of depression, suspecting factors such as genetics, stress, environmental or social events, physical illnesses, and even possible maternal infections during pregnancy.
- Genes thought to be associated with depression include those that contribute to the development of chemical neurotransmitters and those that sustain neurons and synapses.
- Stress has been found to induce neuronal plasticity in the brain, affecting functional connectivity and synapses, but it is thought that chronic stress plays a role in the onset of mental disorders.
- Last month, the FDA approved a version of Ketamine Nasal Spray intended for abbreviated use by people suffering from treatment-resistant depression and offered only in certified environments, due to concerns about possible side effects, addiction and lack of knowledge about how it works.
Driving the news: For this new study, the research team essentially conducted two experiments after the first one had yielded unexpected results, said the study's author, Conor Liston, to Axios.
The first experience compared the timeline of the formation of new spines in neurons to the effect on behavior after ketamine administration.
- They found that "synapse formation is important … but not as we thought," said Liston, an associate professor of neuroscience and psychiatry at Cornell University.
- Ketamine had a positive effect on depression and resulted in increased neuronal activity in about 3 hours, but new synapses did not form in the brain until 12 hours later, he adds. Ketamine therefore seemed to do something to relieve the symptoms almost immediately, regardless of the reconstruction of some synapses.
"This led to the second series of experiments," Liston says.
- They partnered with the University of Tokyo, which has developed a new imaging tool to monitor dendritic spines in mouse neurons, which have been stressed to produce similar reactions to depression in humans. 39; man.
- Stress caused the mice to lose synapses in their brains, but these were largely restored after ketamine administration, says Liston. The tool then cleared the newly formed synapses to see how the behavior was changing – and the mice returned to their previous "depressed" behavior.
- Liston indicates that the results indicate that the antidepressant effect of ketamine could last longer if interventions could be created that strengthen and protect the new synapse formation.
What they say: External experts told Axios that the study revealed important processes.
- David Olson, Assistant Professor at UC Davis, states that FDA approval of ketamine for TRD "is an important step for the field of neuropsychiatry, as ketamine seems to work via a mechanism distinct from traditional antidepressants. as [this one] are absolutely essential to understand the innovative mechanism of action of ketamine in order to be able to develop new generation versions of ketamine even safer and more effective. "
- Ronald Duman, Professor of Psychiatry and Neuroscience at Yale University, says: "The results demonstrate a lag time in the formation of synapse compared to an increase in activity together, as well as behavioral responses of antidepressants effects of ketamine, while increased formation of the spine contributes to the sustained antidepressive actions of ketamine. "
caveat: Liston says the team attempted to mimic human depression in mice using two types of stressed animal models, both of which exhibited similar reactions, but he acknowledges that the system is not perfect.
- Duman agrees: "Translating rodent studies to humans is always difficult and needs to be done with caution," but notes that previous research – including his own – has also associated a reduction in synapses to chronic stress by imaging and autopsies.
- He adds that it will be "important in future studies to measure backbone formation in [medial prefrontal cortex] determine if the same temporal evolution is observed in this region, which is more closely associated with the measured behavioral effects. "
The big picture: Anna Beyeler, neuroscientist at INSERM, wrote an accompanying article in Science say the results "are crucial not only to understand the action of [ketamine] but also for the development of more innovative strategies to treat patients with major depression resistant to treatment. "
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