A Translational Neuroscience Approach to Understanding the Development of Social Anxiety Disorder and Its Pathophysiology

Abstract

This review brings together recent research from molecular, neural circuit, animal model, and human studies to understand the neurodevelopmental mechanisms underlying Social Anxiety Disorder (SAD). SAD is common, debilitating, and often leads to further psychopathology. Numerous studies demonstrate that extremely behaviorally inhibited and temperamentally anxious young children are at marked risk to develop SAD. Recent work in human and nonhuman primates has identified a distributed brain network that underlies early-life anxiety including: central nucleus of the amygdala, anterior hippocampus and orbitofrontal cortex. Moreover, studies in nonhuman primates demonstrate that alterations in this circuit are trait-like in that they are stable over time and across contexts. Importantly, the components of this circuit are differentially influenced by heritable and environmental factors and specific lesion studies demonstrate a causal role for multiple components of the circuit. Molecular studies in rodents and primates are pointing to disrupted neurodevelopmental and neuroplastic processes within critical components of the early-life dispositional anxiety neural circuit. The possibility of identifying an early-life at-risk phenotype, along with an understanding of its neurobiology, provides an unusual opportunity to conceptualize novel preventive intervention strategies aimed at reducing the suffering of anxious children and preventing them from developing further psychopathology.

Intergenerational neural mediators of early-life anxious temperament

“…Specifically, our composite measure of AT was operationalized as the mean of the monkey's relative freezing levels, inhibition of coo vocalizations, and plasma cortisol concentration (15)(16)(17)(18). In humans, the features of AT, extreme behavioral inhibition, and heightened cortisol levels are early risk factors for the later development of anxiety and depressive disorders (6,(19)(20)(21). Children who respond to strangers and novel situations with excessive apprehension or physiological arousal are likely to modify their behavior in ways that are maladaptive and over time are indicative of stress-related psychopathology.…”

“…Children who respond to strangers and novel situations with excessive apprehension or physiological arousal are likely to modify their behavior in ways that are maladaptive and over time are indicative of stress-related psychopathology. Similar to humans, monkeys with extreme AT appear to be functionally impaired across laboratory and naturalistic social settings, making the rhesus monkey model of AT ideal for understanding the pathophysiology that underlies the risk to develop anxiety and depression (21).…”

“…Interestingly, this circuit, genetically correlated with individual differences in early-life anxiety, incorporates survival-related regions that span evolutionary history, where selective pressures shaped each stage of central nervous system development. The OPro/AI, BST, and PAG working together may also underlie the pathophysiology of anxiety and affective disorders (21,30,31). The primate OPro and AI are thought to be involved in predicting and maintaining affective representations of current and future events, which can be communicated to other AT-related brain regions to guide emotional responding (25,32,33).…”

Hjärnan formas av psykologisk behandling

“…Aetiological models of SAD suggest that the risk of developing SAD is a result of an on-going inter-play between cognitions, behaviour and genetics (Fox & Kalin, 2014;Ollendick & Hirshfeld-Becker, 2002;Rapee & Spence, 2004;Stein, 1998;Wong & Rapee, 2016). For instance, overprotective parenting may reinforce the child's anxious cognitions (Rapee & Heimberg, 1997), and having a family member with SAD is associated with a two-to three-fold risk increase for SAD (Tillfors, Furmark, Ekselius, & Fredrikson, 2001a).…”

A Survey of Technologies for Brain Computer Interface Developments to Treat Neuropsychiatric Disorders

“…It is becoming increasingly clear that there is not one single genetic cause, nor a single dysregulated brain region that stands at the root of any psychopathology. Instead we are beginning to understand that psychopathology can develop through a large number of genetic pathways and distributed brain networks (Akil et al 2010;Fox and Kalin 2014). Kay Tye notes that shifting the focus to circuit level therapeutics will significantly transform the quality of mental health care (Tye 2014).…”