The hypothalamus is directly innervated by neuronal systems that produce neurotransmitters, such as serotonin (5-HT), dopamine and norepinephrine (NE), that are involved in mood regulation and play various other roles in cognitive health. During the acute stress crisis, the mesolimbic dopaminergic reward system is stimulated to help maintain morale. However, during chronic stress or depression, the reward system is down-regulated by stress mediators, resulting in anhedonia.…


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Glutamate (L-glutamic acid) and GABA (gamma-aminobutyric acid) are, respectively, the principal excitatory and inhibitory neurotransmitters in the CNS and play a significant role in HPA axis function and mood. These two amino acid-based neurotransmitters account for over 50% of the synapses in the brain, while the monoamines (serotonin, norepinephrine and dopamine) account for only about 5%.…


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When we talk about “stress,” or allostatic load, in terms of the perception of an event, we must realize that these “events” must first be translated into neurochemical signals before they trigger the HPA axis. Therefore, the sensitivity and outcome of translating these events (whether they are ongoing events, memories of past events, or stressful anticipation of unrealized events), is highly dependent upon signaling from other neurotransmitters.…


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When clinicians measure salivary cortisol and DHEA (DHEA-S) to assess stress and HPA axis function, it is common to find DHEA levels below the reference range in a number of individuals. A common explanation for the depletion of DHEA and other hormones (e.g., progesterone, testosterone) due to chronic stress is the phenomenon known as "pregnenolone steal." The pregnenolone steal notion states that…


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Sometimes, when we endeavor to understand and describe complicated medical topics, there is a temptation to find a simple explanation to cut through the complexity. These explanations can help bridge the knowledge gap for a while, but as our knowledge grows, they lose some of their original usefulness (e.g., the notion of “good” and “bad” cholesterol). In some cases, those over-simplified…


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