Selective serotonin reuptake inhibition increases noise burst-induced unconditioned and context-conditioned freezing

ObjectiveWhereas long-term administration of selective serotonin reuptake inhibitors (SSRIs) is effective for the treatment of anxiety disorders, acute administration of these drugs may exert a paradoxical anxiogenic effect. The aim of the present study was to explore the possible effect of an SSRI in situations of unconditioned or limited conditioned fear.MethodsMale Sprague Dawley rats were administered a single dose of an SSRI, escitalopram, before acquisition or expression of context conditioned fear, where noise bursts were used as the unconditioned stimulus. Freezing was assessed as a measure of unconditioned fear (=the acute response to noise bursts) or conditioned fear (=the response to the context), respectively.ResultsNoise bursts elicited an acute increase in freezing but no robust conditioned response 7 days after exposure. Administration of escitalopram before testing exacerbated the freezing response during presentation of the unconditioned stimulus and also unmasked a conditioned response; in contrast, administration of escitalopram prior to acquisition did not influence the conditioned response.ConclusionThe data suggest that freezing in rats exposed to a stimulus inducing relatively mild fear may be enhanced by acute pretreatment with an SSRI regardless of whether the freezing displayed by the animals is an acute unconditioned response to the stimulus in question or a conditioned response to the same stimulus.

Heart rate after trauma and the specificity of fear circuitry disorders

BackgroundFear circuitry disorders purportedly include post-traumatic stress disorder (PTSD), panic disorder, agoraphobia, social phobia and specific phobia. It is proposed that these disorders represent a cluster of anxiety disorders triggered by stressful events and lead to fear conditioning. Elevated heart rate (HR) at the time of an aversive event may reflect strength of the unconditioned response, which may contribute to fear circuitry disorders.MethodThis prospective cohort study assessed HR within 48 h of hospital admission in 602 traumatically injured patients, who were assessed during hospital admission and within 1 month of trauma exposure for lifetime psychiatric diagnosis. At 3 months after the initial assessment, 526 patients (87%) were reassessed for PTSD, major depressive disorder, panic disorder, agoraphobia, social phobia, obsessive compulsive disorder and generalized anxiety disorder.ResultsAt the 3-month assessment there were 77 (15%) new cases of fear circuitry disorder and 87 new cases of non-fear circuitry disorder (17%). After controlling for gender, age, type of injury and injury severity, patients with elevated HR (defined as ⩾96 beats per min) at the time of injury were more likely to develop PTSD [odds ratio (OR) 5.78, 95% confidence interval (CI) 2.32–14.43], panic disorder (OR 3.46, 95% CI 1.16–10.34), agoraphobia (OR 3.90, 95% CI 1.76–8.61) and social phobia (OR 3.98, 95% CI 1.42–11.14). Elevated HR also predicted new fear circuitry disorders that were not co-morbid with a non-fear circuitry disorder (OR 7.28, 95% CI 2.14–24.79).ConclusionsThese data provide tentative evidence of a common mechanism underpinning the onset of fear circuitry disorders.