Abstract
Pregabalin has shown promise in the treatment of anxiety disorders. Previous functional magnetic resonance imaging (fMRI) studies indicate agents used to treat anxiety, e.g., SSRIs and benzodiazepines, attenuate amygdala, insula, and medial prefrontal cortex (mPFC) activation during emotional processing. Our prior study has shown that during anticipation of an emotional stimulus, pregabalin attenuates amygdala and insula activation but increases medial PFC activation. In this study, we examined whether, similar to SSRIs and benzodiazepines, pregabalin attenuates amygdala, insula, and medial PFC during emotional face processing. Sixteen healthy volunteers underwent a double-blind within-subjects fMRI study investigating effects of placebo, 50 mg, and 200 mg pregabalin on neural activation during an emotional face-matching task. Linear mixed model analysis revealed that pregabalin dose-dependently attenuated left amygdala activation during fearful face-matching and left anterior insula activation during angry face-matching. The 50 mg dose exhibited more robust effects than the 200 mg dose in the right anterior insula and ventral ACC. Thus, pregabalin shares some similarity to SSRIs and benzodiazepines in attenuating anger and fear-related insula and amygdala activation during emotional face processing. However, there is evidence that a subclinical 50 mg dose of pregabalin produced more robust and widespread effects on neural responses in this paradigm than the more clinically relevant 200 mg dose. Taken together, pregabalin has a slightly different effect on brain activation as it relates to anticipation and emotional face processing, which may account for its unique characteristic as an agent for the treatment of anxiety disorders.
Highlights
Anxiety disorders affect approximately one in five adults each year in the United States (Kessler et al, 2005) and are associated with significant psychological and somatic distress as well as increased healthcare costs for those afflicted (Hoffman et al, 2008; Bereza et al, 2009; Johnston et al, 2009; Pirkola et al, 2009)
arterial spin labeling (ASL) ANALYSIS Results from Linear mixed effects (LME) analysis investigating effects of pregabalin on cerebral blood flow (CBF) have been reported previously for this cohort (Aupperle et al, 2011) and showed PGB to be associated with increased CBF within the left ventral anterior cingulate cortex (ACC) only [F(2, 24) = 6.803, p < 0.005, −12, 40, 2; post-hoc test revealed 50 mg > PLB]
CBF was www.frontiersin.org extracted for each cluster identified as significant in the functional magnetic resonance imaging (fMRI) regions of interest (ROIs) analyses discussed above to investigate correlations with fMRI Percent signal change (PSC). For those ROI clusters identified as being significantly influenced by dose effect for angry, fear, or happy face-matching, there were no correlations between ASL, CBF, and PSC
Summary
Anxiety disorders affect approximately one in five adults each year in the United States (Kessler et al, 2005) and are associated with significant psychological and somatic distress as well as increased healthcare costs for those afflicted (Hoffman et al, 2008; Bereza et al, 2009; Johnston et al, 2009; Pirkola et al, 2009). Benzodiazepines have a more immediate effect on symptoms, but are associated with concerns regarding side effects such as sedation and cognitive impairment, as well as potential risks for abuse or dependence (McIntosh et al, 2004; Cloos and Ferreira, 2009) Considering these issues, there remains considerable room to improve both the effectiveness and side effect profile of pharmacologic anxiety treatment. The anxiolytic effects observed for PGB may, relate to its eventual effects on neurotransmitter systems (e.g., serotonin, GABA) that have been implicated in Frontiers in Human Neuroscience www.frontiersin.org
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