Gene expression in the primate orbitofrontal cortex related to anxious temperament.

Anxiety disorders are among the most prevalent psychiatric disorders, causing significant suffering and disability. Relative to other psychiatric disorders, anxiety disorders tend to emerge early in life, supporting the importance of developmental mechanisms in their emergence and maintenance. Behavioral inhibition (BI) is a temperament that emerges early in life and, when stable and extreme, is linked to an increased risk for the later development of anxiety disorders and other stress-related psychopathology.

Prefrontal influences on the function of the neural circuitry underlying anxious temperament in primates.

Anxious temperament, characterized by heightened behavioral and physiological reactivity to potential threat, is an early childhood risk factor for the later development of stress-related psychopathology. Using a well-validated nonhuman primate model, we tested the hypothesis that the prefrontal cortex (PFC) is critical in regulating the expression of primate anxiety-like behavior, as well as the function of subcortical components of the anxiety-related neural circuit. We performed aspiration lesions of a narrow 'strip' of the posterior orbitofrontal cortex (OFC) intended to disrupt both cortex and axons entering, exiting and coursing through the pOFC, particularly those of the uncinate fasciculus (UF), a white matter tract that courses adjacent to and through this region.

DREADD-mediated amygdala activation is sufficient to induce anxiety-like responses in young nonhuman primates.

Anxiety disorders are among the most prevalent psychiatric disorders, with symptoms often beginning early in life. To model the pathophysiology of human pathological anxiety, we utilized Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in a nonhuman primate model of anxious temperament to selectively increase neuronal activity of the amygdala. Subjects included 10 young rhesus macaques; 5 received bilateral infusions of AAV5-hSyn-HA-hM3Dq into the dorsal amygdala, and 5 served as controls.

The prefrontal cortex, pathological anxiety, and anxiety disorders.

Anxiety is experienced in response to threats that are distal or uncertain, involving changes in one's subjective state, autonomic responses, and behavior. Defensive and physiologic responses to threats that involve the amygdala and brainstem are conserved across species. While anxiety responses typically serve an adaptive purpose, when excessive, unregulated, and generalized, they can become maladaptive, leading to distress and avoidance of potentially threatening situations.

Nonhuman Primate Models to Explore Mechanisms Underlying Early-Life Temperamental Anxiety.

Anxiety disorders are among the most prevalent psychiatric disorders, causing significant suffering and disability. Behavioral inhibition is a temperament that is linked to an increased risk for the later development of anxiety disorders and other stress-related psychopathology, and understanding the neural systems underlying this dispositional risk could provide insight into novel treatment targets for anxiety disorders. Nonhuman primates (NHPs) have anxiety-related temperaments that are similar to those of humans with behavioral inhibition, facilitating the design of translational models related to human psychopathology.