1. Behavioral Inhibition as a Temperamental Vulnerability to Psychopathology Chapter 7 Jerome Kagan

2. HISTORICAL CONTEXT Eighteenth and 19th centuries restricted the referent for psychopathology to a small number of deviant profiles who were regarded as biologically distinct from the rest of the population. Freud explained that anxiety was between the biology that was presumed to be the primary foundation of symptoms and the individual’s thoughts, behaviors, and emotions. He insisted that the child’s early experiences, especially those within the family, made an important contribution to psychological symptoms. Presently, the emergence of psychopathology requires a biological vulnerability, usually but not always inherited, combined with an acute trauma, chronic stress, or disadvantaged position in society.

3. CONCEPTUAL ISSUES Four conceptual issues penetrate research on the conditions that lead to pathology: The number and exact nature of biological vulnerabilities (diatheses) The number and types of experiential risks (stressors) encountered The most fruitful categories for psychopathology Evidence used to infer the constructs for risk and pathology

4. THE ETIOLOGICAL ROLE OF TEMPERAMENTS Genes, Neurochemistry, and Temperaments Molecules that, along with the density and locations of their receptors, have the potential to influence the feelings and behaviors that define human temperaments including: Norepinephrine Dopamine Pinephrine Serotonin Corticotropin releasing hormone (CRH) Glutamate Gamma aminobutyric acid (GABA) Opioids Vasopressin Oxytocin Prolactin Monoamine oxidase (MAO) Sex hormones androgen and estrogen

5. THE ETIOLOGICAL ROLE OF TEMPERAMENTS Reactions to the Unexpected or Unfamiliar Two biases that have been studied more extensively than others are: Behaviorally inhibited: Children who show restrained, cautious, avoidant reactions to unfamiliar objects, people, or settings. Uninhibited: Children displaying spontaneous approach to the same events. High- and Low-Reactive Infants Child and early adolescent evaluations Age 18 assessments

6. THE ETIOLOGICAL ROLE OF TEMPERAMENTS Particular genetic polymorphisms make small contributions to behavioral inhibition, especially when combined with particular experiences. Possession of the short allele of the 5-HTTLPR gene, combined with the experience of stress during childhood, especially severe maltreatment, increases by a small amount the risk for persistent adult depression (Karg, Burmeister, Shedden & Sen, 2011; Uher et al., 2011).

7. THE ETIOLOGICAL ROLE OF TEMPERAMENTS Adults with 2 or 5 rather than 7 repeats in the DRD4 receptor gene are high in novelty seeking but, surprisingly, individuals from economically disadvantaged backgrounds with the same polymorphisms are not (Eley et al., 2004; Caspi et al., 2003; Kaufman et al., 2004; Lahti et al., 2006). High- and Low-Reactive Infants Primary functions of the amygdala are to respond to all unfamiliar or unexpected events and to generate an initial state of vigilance and preparation for action when the event poses a threat (Fitzgerald et al., 2006). Infants with excitable amygdalae should be more likely than others to become inhibited children.

8. THE ETIOLOGICAL ROLE OF TEMPERAMENTS Longitudinal study to discover patterns of infant behaviors that might predict the inhibited and uninhibited profiles that appear later in life: High reactive: 20% of the infants showed a pattern that combined high levels of limb activity, back arching, and crying. Low Reactive: 40% percent showed a pattern of minimal motor activity, few arches, and little crying. Child and early adolescent evaluations High-reactives assessed at 14 and 21 months were significantly more avoidant of and fearful to a series of unfamiliar social and nonsocial incentives than low reactives. However, about 20% of the high reactives were not highly fearful at both ages because, we presume, their experiences allowed them to gain some control of the public expression of signs of fear.

9. THE ETIOLOGICAL ROLE OF TEMPERAMENTS Child and early adolescent evaluations At age 7 years about half of the high reactives possessed fears of animals, the dark, thunder storms, and/or unfamiliar people and places, compared with fewer than 10% of low reactives. At 11 and 15 years high reactives were not only quieter and emotionally more subdued, but they also showed few spontaneous smiles during laboratory sessions designed to measure four biological reactions that are indirect signs of a more excitable amygdala. More high- than low reactives showed a larger brain stem auditory evoked response from the inferior colliculus at both 11 and 15 years.

10. THE ETIOLOGICAL ROLE OF TEMPERAMENTS Age 18 assessments The high- and low reactives differed significantly on three biological measures: High reactives had a thicker cortex in a small region in the ventromedial prefrontal cortex (vmPFC) of the right hemisphere. High reactives showed a larger surge of blood flow (the BOLD signal) to the right amygdala the first time they saw a set of angry faces they did not expect. High reactives showed a shallower slope of habituation of the BOLD signal to the left amygdala to repeated presentations of ecologically invalid scenes. Significantly higher prevalence of depression, social phobia, and/or general anxiety disorder among high reactives than low-reactives

11. SYNTHESIS Investigators should be sensitive to the contexts of observation, a requirement that applies to the source of evidence used for inferences. Investigators should base their inferences on patterns of variables, not single measures. Hyping Biology The current emphasis on the biological contribution has considerable value. But it has two serious disadvantages. It fails to raise public consciousness over the contributions of the many adults and peers whose interactions with a particular child can place that youth at risk for pathology. It motivates a single-minded approach to finding risk genes and drug cures for all disorders and fails to motivate clinicians to consider combining medicines with strategies that might alter the child’s circumstances.