Stress, Anxiety, and Serotonin
The early-life stress of maternal separation is associated with enhanced serotonin type 2 (5-HT2) receptor function, perturbation of neuronal circuit responses to stress and increased anxiety behavior. Benekareddy et al.
(pages 1024–1032) now provide evidence that treatment with ketanserin, a 5-HT2 receptor antagonist, prevents the development of anxiety-related behavior and dysregulated gene expression in the prefrontal cortex observed in maternally separated rats.
Murrough et al.
(pages 1033–1038) report reduced serotonin transporter availability within the amygdala in patients with posttraumatic stress disorder (PTSD) using positron emission tomography and the novel serotonin transporter-selective radiotracer [11
C]AFM. Lower serotonin transporter availability was associated with higher levels of anxiety and depression symptoms in PTSD patients. These results provide novel evidence for abnormalities in the serotonin transporter and amygdala function in PTSD.
Serotonin 1B (5-HT1B) receptor agonists exacerbate obsessive-compulsive disorder (OCD) symptoms in patients and induce OCD-like behavior in mice. Shanahan et al.
(pages 1039–1048) show that orbitofrontal 5-HT1B receptors are necessary and sufficient to induce OCD-like behavior in mice, and that serotonin reuptake inhibitor pharmacotherapy reduces OCD-like behavior by desensitizing orbitofrontal 5-HT1B receptors. These findings suggest an essential role for orbitofrontal 5-HT1B receptors in OCD pathophysiology and treatment.
Attention bias modification, a technique to alter cognitive biases, is used as a therapy for anxiety disorders. Fox et al.
(pages 1049–1054) randomized healthy adults to receive either positive bias or negative bias training. They found that individuals with a low-expression form of 5-HTTLPR, the serotonin transporter gene, relative to those with the high-expression form, developed stronger biases regardless of training type, suggesting that allelic variation influences differential sensitivity to interventions.
Brain Alterations in Fear and Anxiety
Zarei et al.
(pages 1083–1090) performed a structural and diffusion tensor magnetic resonance imaging study of pediatric-onset OCD to explore whether it constitutes a neurobiologically or clinically different subtype of OCD. Adolescents with OCD displayed a wide range of changes in gray matter, white matter, and subcortical structures compared to adolescent controls. These changes are broadly consistent with, but more extensive than, those identified in the adult OCD literature.
PTSD is associated with anterior cingulate cortex (ACC) abnormalities, which may in turn be associated with deficits in emotion regulation. The Val158Met polymorphism in the catechol-O
-methyltransferase gene, which regulates dopamine in the frontal lobe, may moderate ACC integrity in PTSD. Schulz-Heik et al.
(pages 1091–1096) tested this hypothesis in Vietnam and Persian Gulf War veterans with or without PTSD. Their findings indicate that the polymorphism moderates the effect of PTSD-related processes on ACC volume.
© 2011 Published by Elsevier Inc. All rights reserved.