The vast range of human emotional experiences represents broad individuality and robust personality distinction. Experiencing a balanced emotional range supports general well-being, but some individuals are prone to higher levels of baseline anxiety and neuroticism, which can in turn become vulnerabilities to depression or other mood disorders. Understanding if there is an underlying molecular signature of high trait anxiety can lead to insight into how individual genetic, epigenetic, or developmental differences can lead to variance in mood disorder susceptibility or can inspire individualized treatments for those with mood disorders. In the current issue of Biological Psychiatry, Gebara et al.(1) explore the relationship between individual differences in anxiety-like behaviors and both the expression of mitochondrial genes and mitochondrial function in the nucleus accumbens (NAc).

Anxiety and depression are linked to functional changes in brain reward circuits, specifically in the NAc (2). NAc medium spiny neurons (MSNs) are the primary projection outputs from this region. Changes in their neuronal structure, excitability, and output are linked to changes in most reward-related behaviors, including those related to anxiety and depression in humans (2). NAc is a central node for individual differences in gene expression associated with susceptibility or resilience to chronic stress in mice (3). MSNs in the NAc are dynamically plastic in response to reward learning or to stress, increasing or decreasing dendritic complexity and dendritic spine density to support changes in neuronal excitability or output (2). The dependence of such dynamic remodeling on mitochondrial function, mitochondrial-dependent Ca2+ buffering, and available cellular energy is rapidly being explored in various neuronal subtypes, such as NAc MSNs. Gebara et al.(1) contribute to the small but growing literature examining mitochondrial function in the context of anxiety and mood disorders (4).