br Beyond extinction cognitive forms

Beyond extinction: cognitive forms of fear regulation While the efficacy of exposure-based CBT depends on the ability of a given individual to acquire and retrieve extinction memories (Berry et al., 2009), cognitive strategies can also be employed to regulate conditioned fear responding. Standard CBT protocols generally include a cognitive component in which patients are directed to strategically reframe anxiety-provoking situations in order to reduce the negative emotional responses that these situations elicit (Beck et al., 1985). One form of cognitive regulation is emotional reappraisal, in which an automatic emotional response to an emotional event is controlled through conscious transformation of its meaning (Gross, 2001). Human fMRI studies have shown that successful reappraisal of negatively valenced stimuli is dependent upon recruitment of prefrontal and cingulate regions associated with cognitive control (Ochsner et al., 2004). However, the prefrontal Aminoallyl-dUTP is still maturing into early adulthood, suggesting that children and adolescents might show diminished reappraisal capacity compared to adults. Recent studies have presented some evidence to this effect, with reappraisal success positively correlating with age across adolescence (Silvers et al., 2012; McRae et al., 2012). Although only a small number of studies have examined reappraisal of threat across development, future pre-clinical research that tests different forms of reappraisal across childhood and adolescence will help shed light on which reappraisal strategies might be most effective at any given developmental stage. Another important cognitive factor mediating fear regulation is attentional control. The ability to increase attention to threat stimuli is an adaptive function that facilitates the detection of danger (LeDoux, 2000). However, devoting an inappropriate amount of attentional resources to non-significant or low-level threats can be maladaptive. This notion is supported by research providing strong evidence for a positive correlation between threat-related attentional bias and anxiety (Bar-Haim et al., 2007; Mathews and MacLeod, 1985; Monk et al., 2008). Emerging data suggests that reductions in attentional threat bias can be achieved through attentional bias modification therapy (Hakamata et al., 2010; Bar-Haim, 2010; MacLeod and Mathews, 2012), which involves teaching individuals to shift attention away from threat-related stimuli through repetitive, computer-based training (MacLeod, 1995; MacLeod and Mathews, 2012). While attentional bias modification therapy has been shown to lead to decreases in threat bias as well as diminished anxiety symptoms (Hakamata et al., 2010), treatment outcomes across studies are inconsistent (Mogoaşe et al., 2014), suggesting further research will be necessary in order to optimize these techniques and determine when, and for whom, attention-based therapy will be most beneficial.
Implications for novel treatments: where do we go from here? Pharmacological interventions offer one alternative approach. d-Cycloserine (DCS) has been shown to enhance extinction retrieval in adolescent and adult rats (McCallum et al., 2010; Baker et al., 2012). Serotonin selective reuptake inhibitors (SSRIs) have demonstrated similar results, with one study showing that chronic administration of SSRIs in combination with extinction training prevented the return of fear in mice (Karpova et al., 2011; Deschaux et al., 2011). While these results are promising, non-pharmacological approaches may be preferable when treating the developing brain. Rodent studies have demonstrated that adolescents can benefit from an increased number of exposure trials during extinction (McCallum et al., 2010). However, this approach may not be ideal for adolescents with anxiety disorders as it would require additional time and money and could lead to higher attrition rates and increased failure to complete treatment.