Published: Apr 1, 2019 by Chloe
Chronic stress exposure is associated with the development and onset of neuropsychiatric disorders like anxiety and depression. These disorders are frequently identified has having an inherent sex bias, where females present with symptoms at higher rates than males. Understanding the mechanistic connections between chronic stress exposure and affective disorders, particularly with regards to sex differences, is imperative for developing effective prevention and intervention strategies. The prefrontal cortex is a promising area of investigation, as this brain region is stress-responsive in a sex-specific manner and is critically involved in emotional behaviors and functioning. The prefrontal cortex relies on a balance between excitatory and inhibitory neurotransmission for emotional functioning, and emotional disorders and chronic stress involve perturbations in this excitatory/inhibitory (E/I) balance.
E/I balance arises from a complex interplay between excitatory and inhibitory neuronal subtypes. Chronic stress perturbs E/I balance and thus contributes to emotional dysfunction. Parvalbumin cells are a subtype of inhibitory neuron that keeps excitatory neurotransmission in check to help maintain healthy E/I balance and prefrontal cortex-related emotional behaviors. My research proposes and investigates the hypothesis that chronic stress increases the activity of prefrontal parvalbumin neurons, leading to over-inhibition and hypoactivity of the prefrontal cortex, impairing its ability to regulate emotional behaviors. This phenomenon occurs predominately in females and is related to increased anxiety, suggesting sex-specific mechanisms for stress-induced emotional dysfunction.
According to this hypothesis of over-inhibition in the prefrontal cortex, therapeutic interventions for disorders like anxiety and depression may involve reducing prefrontal inhibition and enhancing excitability to restore functional E/I balance and healthy emotional behaviors. In addition to being involved in the stress response, E/I balance during stress may also mediate resilience vs. vulnerability to stress and thus may be a target for preventative measures. It is the hope that this research can help inform the development of such preventative and therapeutic interventions, and that treatments for anxiety and depression will continue to integrate safe, effective pharmaceuticals to target biological mechanisms with psychotherapy to target past and present sources of stress.
