The nature of individual differences in inhibited temperament and risk for psychiatric disease: A review and meta-analysis

Abstract

What makes us different from one another? Why does one person jump out of airplanes for fun while another prefers to stay home and read? Why are some babies born with a predisposition to become anxious? Questions about individual differences in temperament have engaged the minds of scientists, psychologists, and philosophers for centuries. Recent technological advances in neuroimaging and genetics provide an unprecedented opportunity to answer these questions. Here we review the literature on the neurobiology of one of the most basic individual differences-the tendency to approach or avoid novelty. This trait, called inhibited temperament, is innate, heritable, and observed across species. Importantly, inhibited temperament also confers risk for psychiatric disease. Here, we provide a comprehensive review of inhibited temperament, including neuroimaging and genetic studies in human and non-human primates. We conducted a meta-analysis of neuroimaging findings in inhibited humans that points to alterations in a fronto-limbic-basal ganglia circuit; these findings provide the basis of a model of inhibited temperament neurocircuitry. Lesion and neuroimaging studies in non-human primate models of inhibited temperament highlight roles for the amygdala, hippocampus, orbitofrontal cortex, and dorsal prefrontal cortex. Genetic studies highlight a role for genes that regulate neurotransmitter function, such as the serotonin transporter polymorphisms (5-HTTLPR), as well as genes that regulate stress response, such as corticotropin-releasing hormone (CRH). Together these studies provide a foundation of knowledge about the genetic and neural substrates of this most basic of temperament traits. Future studies using novel imaging methods and genetic approaches promise to expand upon these biological bases of inhibited temperament and inform our understanding of risk for psychiatric disease.

Keywords: Amygdala; Anxious temperament; Behavioral inhibition; Neuroimaging; Serotonin; Social anxiety disorder.

Figure 1

Approximately 43% of children characterized as having an inhibited temperament (107/246) develop social anxiety disorder by mid-adolescence. In contrast, only about 13% of control children (57/446) develop social anxiety disorder by the same age. Data adapted from (Clauss and Blackford, 2012).

Figure 2

Inhibited temperament is associated with alterations in a complex neurocircuit, including the amygdala, basal ganglia, and prefrontal regions.

Figure 3

Based on a meta-analysis of 13 functional MRI studies of inhibited temperament, inhibited temperament is associated with increased activity in the bilateral amygdala, parahippocampal gyrus, globus pallidus, caudate, and medial frontal gyrus.

Figure 4

The effects of individual brain regions on anxious temperament in rhesus monkeys have been demonstrated by lesioning the amygdala, hippocampus, and orbitofrontal cortex.

Figure 5

Social anxiety disorder has a median age of onset of 13 years and 75% of patients have an onset by age 15 (Kessler et al., 2005a). Published neuroimaging studies of inhibited temperament have focused on imaging adolescents and young adults (blue), who have already reached the median age of onset for social anxiety disorder. Future studies should focus on younger children, who have yet to reach the age of onset for social anxiety disorder to understand how temperament affects brain function.