Trim: 7in × 10in Top: 0.5in Gutter: 0.875in CUUS1847-24 CUUS1847/Armony ISBN: 978 1 107 00111 4 October 14, 2012 18:56 CHAPTER 24 Trait Anxiety, Neuroticism, and the Brain Basis of Vulnerability to Affective Disorder Sonia Bishop & Sophie Forster Studies of the brain basis of “norma- pathways through which risk to affective ill- tive” or “healthy” processing of emotion- ness is conferred. ally salient stimuli have flourished over Understanding the brain basis of vulner- the last two decades. An initial focus on ability to affective disorder goes hand in regions implicated in the detection of emo- hand with a focus on individual variation tionally salient stimuli (Morris et al., 1996; and, in particular, trait differences in the Whalen et al., 1998) has broadened to mechanisms supporting the detection and include discussion of mechanisms support- controlled processing of emotional stimuli. ing regulatory functions (Bishop, Duncan, How do we study trait differences in vul- Brett, & Lawrence, 2004; Davidson, 2002; nerability to anxiety and depressive disor- Ochsner, Bunge, Gross, & Gabrieli, 2002; ders and try to unpack the brain mechanisms Kim, Somerville, Johnstone, Alexander, & though which these might act? A number of Whalen, 2003; Phelps, Delgado, Nearing, & approaches have been adopted, with both LeDoux, 2004). Running in parallel to this shared and unique advantages and limita- literature, psychiatric imaging studies have tions. described alterations in brain function across Studies of the brain basis of vulnerabil- a wide range of anxiety and depressive dis- ity to affective disorders typically rely on orders (for reviews and meta-analyses see recruiting nonclinical volunteer samples and Etkin & Wager, 2007; Ressler & Mayberg, then regressing scores on self-report mea- 2007; Shin & Liberzon, 2010;Stein2009). The sures of trait affect or experience of disorder- study of the brain mechanisms underlying related symptomatology against indices of vulnerability to disorder has, for some rea- brain function or structure. It is important son, fallen outside of the primary spotlight. to remember that this approach is correla- We argue that work of this nature is criti- tional in nature, and hence no conclusions cal to bridging studies in healthy volunteer can be drawn about the direction of causal- and patient groups and to identifying the ity. For example, if we find that, in a student 553 Trim: 7in × 10in Top: 0.5in Gutter: 0.875in CUUS1847-24 CUUS1847/Armony ISBN: 978 1 107 00111 4 October 14, 2012 18:56 554 SONIA BISHOP & SOPHIE FORSTER population, elevated scores on a measure category uses measures taken from the per- of neuroticism are linked to poor frontal sonality literature, such as the Neuroticism recruitment, this could equally plausibly scale from either the Eysenck Personality reflect individuals scoring high on neuroti- Questionnaire (EPQ; Eysenck & Eysenck, cism being less able to cope with envi- 1975) or the NEO Personality Inventory ronmental stress, resulting in diminished (Costa & MacCrae, 1992). The third cat- frontal function; individuals with compro- egory focuses on genetic markers that mised frontal function being more likely differ among individuals (functional poly- to develop a neurotic personality style; morphisms with two or more common vari- both elevated neuroticism and compro- ants) and that have been linked to differ- mised frontal function stemming from a pri- ences in affect-related behaviors in humans mary disruption to neurotransmitter func- and other species. In this chapter, we focus tion; or all of these factors in combination. on the first two of these categories, com- There are also important methodological menting only briefly on the third (for issues pertaining to good practice in con- further discussion, see Chapter 25). The ducting correlational analyses of brain activ- majority of studies on the brain basis of vul- ity, which are discussed briefly later in the nerability to affective disorder falling within chapter. these categories have used measures of trait A shared positive feature of studies in this anxiety (category 1) or neuroticism (cate- area is that constructs such as trait anxiety or gory 2). We use these examples to explore neuroticism can be examined as continuous the state of the field as it stands and to factors, facilitating exploration of their lin- address outstanding questions for future ear and nonlinear relationships with regional research. brain activity. This allows for a more com- plex and potentially accurate picture to be drawn than one that solely uses DSM cat- Trait Anxiety and Neuroticism: egorical assessments of the binary presence Indexing Vulnerability to Affective or absence of a given disease state; the lat- Disorders through Self-Report ter “diagnostic” approach faces limitations arising from difficulties in applying cate- The trait subscale of the Spielberger State gorical cutoffs, high comorbidity between Trait Anxiety Inventory (Spielberger et al., many anxiety and depressive disorders, and 1983) is a widely used measure of trait poor diagnostic reliability (Brown & Barlow, propensity to anxiety. It has been shown 2009). to have good concurrent validity, with Studies of the brain basis of vulnerabil- patients with anxiety disorders (ADs) scor- ity to affective disorder can be categorized ing higher on the STAI trait subscale than according to the measure used to assess controls (Bieling, Antony, & Swinson, 1998). individual differences in trait affective style. Although fewer studies have examined pre- Arguably there are three main categories. dictive validity, pretrauma STAI trait scores The first involves measures derived from have been found to predict levels of post- the clinical literature and normed for use traumatic stress disorder symptomatology in nonclinical populations to assess individu- after trauma (Weems et al., 2007). How- als’ tendency to show disorder-related symp- ever, the STAI has been criticized for having tomatology, affective and cognitive styles. poor discriminative validity, with individu- A prominent example is the Spielberger als with major depressive disorder (MDD) State Trait Anxiety Inventory (STAI; Spiel- also showing elevated scores on the trait berger, Gorsuch, Lushene, Vagg, & Jacobs, subscale (Mathews, Ridgway, & Williamson, 1983), widely used in studies of the cog- 1996). One possibility is that this low dis- nitive correlates of trait anxiety within criminant validity reflects a poor choice nonselected student samples. The second of anxiety-specific items for the scale. A Trim: 7in × 10in Top: 0.5in Gutter: 0.875in CUUS1847-24 CUUS1847/Armony ISBN: 978 1 107 00111 4 October 14, 2012 18:56 TRAIT ANXIETY, NEUROTICISM, AND THE BRAIN BASIS OF VULNERABILITY TO AFFECTIVE DISORDER 555 second is that there is genuine shared vari- ance underlying vulnerability to both ADs and MDD. Not only are STAI trait scores elevated in patients with MDD but scores on this and other anxiety scales, such as the Tay- lor Manifest Anxiety Scale (Taylor, 1953), have also been found to correlate highly with scores on self-report measures of depres- sive symptomatology; for example, the Beck Depression Inventory (BDI; Beck Ward, Mendelson, Mock, & Erbaugh, 1961)and personality indices of neuroticism (Luteijn & Bouman, 1988). Neuroticism is charac- terized by a propensity for negative affect (Watson & Clark, 1984). This trait, measured by widely used instruments such as the NEO Personality Inventory and the Eysenck Per- sonality Questionnaire, has emerged over the last century as one of the most widely studied personality traits (Costa & Mac- Crae, 1992; Eysenck & Eysenck, 1975; John, 1990). The relationship with vulnerability to affective disorder has arguably been inves- tigated more thoroughly for neuroticism than for any other dimension of personal- ity (Brown, 2007; Brown & Rosellini, 2011, Kendler, Gardner, Gatz, & Pedersen, 2007). There is strong evidence to support not only shared variance but also common genetic influences among neuroticism, anxiety dis- 24 1 orders, and depressive disorders (Hettema Figure . Anxiety, neuroticism and et al., 2008; Kendler et al., 2007). depression: overlapping constructs? Three alternate models. (A). Self-report measures of A likely interpretation of the high corre- anxiety, depression, and neuroticism could lations observed among indices of anxiety, potentially all be tapping the same single depression, and neuroticism is that they tap, underlying trait. (B). Alternatively, anxiety and at least in part, into a common underlying depression might be separate components of the trait (Figure 24.1). According to the popular broader trait of neuroticism. In keeping with this tripartite model, anxiety and depression not perspective, the NEO-PI-R includes anxiety and only have a shared component – a propen- depression as subfactors, or “facets,” of sity to negative affect (which arguably maps neuroticism (Costa & McCrae; 1995). (C). A on to the construct of neuroticism) – but third theoretical stance, represented by Clark 1991 also unique components of anxious arousal and Watson’s ( ) tripartite model, asserts that and anhedonia, respectively (Clark & Wat- anxiety and depression not only have a shared component of negative affect or general distress son, 1991). This conception has led to the (potentially corresponding to the construct of development of the Mood and Anxiety neuroticism) but also unique components of Symptoms Questionnaire (MASQ; Watson “anxious arousal” (autonomic hyperactivity) and & Clark,