Research reportStructural correlates of trait anxiety: Reduced thickness in medial orbitofrontal cortex accompanied by volume increase in nucleus accumbens
Introduction
Personality traits, such as trait anxiety, are regarded as stable and biological predispositions (Rauch et al., 2005). Trait anxiety in normal subjects has been shown to be closely related to pathological anxiety (Chambers et al., 2004) and may increase the risk of psychiatric disorders (Bienvenu et al., 2001). Trait anxiety reflects an individual's disposition to experience anxiety-relevant feelings or thoughts or to show anxiety-related behaviors (Spielberger, 1983). Overall it comprises the tendency to respond fearfully to a wide variety of unspecific stressors (Spielberger, 1972). Since trait anxiety is regarded as a stable factor with a biological underpinning, we set out to explore its structural correlates. Previous volumetric studies on anxiety-related psychiatric disorders have consistently stressed the importance of the medial orbitofrontal cortex (mOFC, sometimes referred to as ventromedial prefrontal cortex). Studies on panic disorder have consistently reported volume reductions in mOFC (Asami et al., 2009, Roppongi et al., 2010, Sobanski et al., 2010). Likewise, a study comparing patients suffering from post traumatic stress disorder (PTSD) with individuals exposed to trauma but not having developed PTSD found diminished medial prefrontal cortex, namely in pregenual anterior cingulate and subcalossal cortex (Rauch et al., 2003). Along the same lines obsessive–compulsive disorder (OCD) has been related to orbitofrontal volume reductions (Szeszko et al., 1999). Although the mOFC is not the only structure for which alterations have been reported in anxiety-related psychiatric disorders, this area is consistently found to be deviant in different types of anxiety spectrum disorders.
On the behavioral level anxiety-related personality factors have been associated with enhanced fear conditionability as well as impaired extinction of learned fear (Barrett and Armony, 2009). In classical Pavlovian fear conditioning a neutral stimulus (conditioned stimulus, CS) comes to be evaluated as threatening due to its association with an aversive stimulus (unconditioned stimulus, UCS) and elicits fear (Pavlov, 1927). In fear extinction it is learned that a CS no longer predicts a noxious UCS to which it had previously been associated, leading to inhibition of the conditioned response (CR). Extinction creates a new CS-nonUCS memory trace that competes with the initial fear (CS-UCS) memory (Myers and Davis, 2002). An overactive neuronal fear circuitry and reduced recruitment of prefrontal control have been proposed as neural correlates of facilitated fear conditioning and reduced extinction (Bishop, 2007). The structures mOFC, nucleus accumbens and amygdala have been associated with fear conditioning in humans and rodents (Gottfried et al., 2002, Pezze and Feldon, 2004) and abnormal activation in nucleus accumbens has been observed in PTSD (Sailer et al., 2008, Vythilingam et al., 2009). Previous studies have related retention of extinction memory to the cortical thickness of mOFC (Milad et al., 2005, Rauch et al., 2005). A path analysis by Rauch et al. (2005) revealed that extinction retention mediates the relationship between mOFC thickness and the personality trait extraversion and suggests a path though which brain structures and personality may be interconnected.
The aim of the present study was to relate inter-individual differences in cortical thickness to inter-individual differences in trait anxiety in a healthy sample. To this end we used surface-based morphology analysis. Moreover aimed at relating the cortical thinning associated with trait anxiety to automatically segmented volumes of subcortical structures that have been implicated in fear conditioning (NAcc, amygdala).
Section snippets
Participants
34 subjects were recruited by means of newspaper advertisements. The participants (20 women and 14 men) had a mean age of 30.5 years (ranging from 19 to 47 years). All subjects were free of medical, neurological, and psychiatric disorders — according to personal interviews (Mini-International Neuropsychiatric Interview, Lecurbier et al., 1997) carried out by a psychiatrist. Subjects with a family history (first degree) of axis I disorder were excluded from participation. In addition, exclusion
Results
Across participants the average trait anxiety score was 29.9 (SD = 5.6). There was no significant difference of trait anxiety scores between male and female participants (p > 0.17). The average depression score measured by means of the BDI was 1.2, ranging from 0 to 6 (SD = 1.8, possible maximum score 63) indicating absence of depression.
When computing a whole brain analysis in order to explore brain regions where cortical thickness varies with trait anxiety (controlling for age and sex), we found a
Discussion
We investigated the structural correlates of trait anxiety in normal subjects. We found a negative correlation between trait anxiety and cortical thickness in the right mOFC, more specifically in gyrus rectus. On the subcortical level we found trait anxiety to be positively correlated with the volume of NAcc but not with amygdala volume. Moreover, left NAcc volume was negatively correlated with cortical thickness in the mOFC.
The location within the mOFC where the reduction of cortical thickness
Role of funding source
The funding agencies had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Conflict of interest
SK is a Postdoctoral Fellow of the Research Foundation Flanders (FWO). JG has received research funding from the German Federal Ministry of Education and Research (BMBF 01GS08159), research funding from AstraZeneca, Eli Lilly & Co, Janssen-Cilag, Bristol-Myers Squibb and speaker fees from AstraZeneca, Janssen-Cilag, and Bristol-Myers Squibb. FS reports no conflict of interest.
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